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Progesterone (P4) is an endogenous steroid and progestogen
sex hormone Sex hormones, also known as sex steroids, gonadocorticoids and gonadal steroids, are steroid hormones that interact with vertebrate steroid hormone receptors. The sex hormones include the androgens, estrogens, and progestogens. Their effect ...
involved in the
menstrual cycle The menstrual cycle is a series of natural changes in hormone production and the structures of the uterus and ovaries of the female reproductive system that make pregnancy possible. The ovarian cycle controls the production and release of eggs a ...
,
pregnancy Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ca ...
, and embryogenesis of humans and other species. It belongs to a group of steroid hormones called the progestogens and is the major progestogen in the body. Progesterone has a variety of important functions in the body. It is also a crucial
metabolic intermediate Metabolic intermediates are molecules that are the precursors or metabolites of biologically significant molecules. Although these intermediates are of relatively minor direct importance to cellular function, they can play important roles in the ...
in the production of other endogenous steroids, including the
sex hormone Sex hormones, also known as sex steroids, gonadocorticoids and gonadal steroids, are steroid hormones that interact with vertebrate steroid hormone receptors. The sex hormones include the androgens, estrogens, and progestogens. Their effect ...
s and the
corticosteroid Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are involv ...
s, and plays an important role in brain function as a neurosteroid. In addition to its role as a natural hormone, progesterone is also used as a medication, such as in combination with
estrogen Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal acti ...
for
contraception Birth control, also known as contraception, anticonception, and fertility control, is the use of methods or devices to prevent unwanted pregnancy. Birth control has been used since ancient times, but effective and safe methods of birth contr ...
, to reduce the risk of
uterine The uterus (from Latin ''uterus'', plural ''uteri'') or womb () is the organ in the reproductive system of most female mammals, including humans that accommodates the embryonic and fetal development of one or more embryos until birth. The ...
or cervical cancer, in
hormone replacement therapy Hormone replacement therapy (HRT), also known as menopausal hormone therapy or postmenopausal hormone therapy, is a form of hormone therapy used to treat symptoms associated with female menopause. These symptoms can include hot flashes, vaginal ...
, and in
feminizing hormone therapy Feminizing hormone therapy, also known as transfeminine hormone therapy, is hormone therapy and sex reassignment therapy to change the secondary sex characteristics of transgender people from masculine or androgynous to feminine. It is a comm ...
. It was first prescribed in 1934.


Biological activity

Progesterone is the most important progestogen in the body. As a potent
agonist An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ago ...
of the nuclear progesterone receptor (nPR) (with an
affinity Affinity may refer to: Commerce, finance and law * Affinity (law), kinship by marriage * Affinity analysis, a market research and business management technique * Affinity Credit Union, a Saskatchewan-based credit union * Affinity Equity Par ...
of KD = 1 nM) the resulting effects on ribosomal transcription plays a major role in regulation of female reproduction. In addition, progesterone is an agonist of the more recently discovered
membrane progesterone receptor Membrane progesterone receptors (mPRs) are a group of cell surface receptors and membrane steroid receptors belonging to the progestin and adipoQ receptor (PAQR) family which bind the endogenous progestogen and neurosteroid progesterone, as well as ...
s (mPRs), of which the expression has regulation effects in reproduction function ( oocyte maturation, labor, and
sperm motility Sperm motility describes the ability of sperm to move properly through the female reproductive tract (internal fertilization) or through water (external fertilization) to reach the egg. Sperm motility can also be thought of as the ''quality'', wh ...
) and cancer although additional research is required to further define the roles. It also functions as a ligand of the PGRMC1 (progesterone receptor membrane component 1) which impacts
tumor progression Tumor progression is the third and last phase in tumor development. This phase is characterised by increased growth speed and invasiveness of the tumor cells. As a result of the progression, phenotypical changes occur and the tumor becomes more agg ...
, metabolic regulation, and viability control of
nerve cells A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. ...
. Moreover, progesterone is also known to be an antagonist of the sigma σ1 receptor, a
negative allosteric modulator In pharmacology and biochemistry, allosteric modulators are a group of substances that bind to a receptor to change that receptor's response to stimulus. Some of them, like benzodiazepines, are drugs. The site that an allosteric modulator binds t ...
of
nicotinic acetylcholine receptor Nicotinic acetylcholine receptors, or nAChRs, are receptor polypeptides that respond to the neurotransmitter acetylcholine. Nicotinic receptors also respond to drugs such as the agonist nicotine. They are found in the central and peripheral ner ...
s, and a potent antagonist of the
mineralocorticoid receptor The mineralocorticoid receptor (or MR, MLR, MCR), also known as the aldosterone receptor or nuclear receptor subfamily 3, group C, member 2, (NR3C2) is a protein that in humans is encoded by the ''NR3C2'' gene that is located on chromosome 4q31 ...
(MR). Progesterone prevents MR activation by binding to this receptor with an affinity exceeding even those of aldosterone and
glucocorticoid Glucocorticoids (or, less commonly, glucocorticosteroids) are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor that is present in almost every verteb ...
s such as cortisol and
corticosterone Corticosterone, also known as 17-deoxycortisol and 11β,21-dihydroxyprogesterone, is a 21-carbon steroid hormone of the corticosteroid type produced in the cortex of the adrenal glands. It is of minor importance in humans, except in the very rar ...
, and produces
antimineralocorticoid An antimineralocorticoid, also known as a mineralocorticoid receptor antagonist (MRA or MCRA) or aldosterone antagonist, is a diuretic drug which antagonizes the action of aldosterone at mineralocorticoid receptors. This group of drugs is ofte ...
effects, such as
natriuresis Natriuresis is the process of sodium excretion in the urine through the action of the kidneys. It is promoted by ventricular and atrial natriuretic peptides as well as calcitonin, and inhibited by chemicals such as aldosterone. Natriuresis lowers t ...
, at physiological concentrations. In addition, progesterone binds to and behaves as a
partial agonist In pharmacology, partial agonists are drugs that bind to and activate a given receptor, but have only partial efficacy at the receptor relative to a full agonist. They may also be considered ligands which display both agonistic and antagonis ...
of the
glucocorticoid receptor The glucocorticoid receptor (GR, or GCR) also known as NR3C1 (nuclear receptor subfamily 3, group C, member 1) is the receptor to which cortisol and other glucocorticoids bind. The GR is expressed in almost every cell in the body and regulates ...
(GR), albeit with very low potency ( EC50 >100-fold less relative to cortisol). Progesterone, through its neurosteroid
active metabolite An active metabolite is an active form of a drug after it has been processed by the body. Metabolites of drugs An active metabolite results when a drug is metabolized by the body into a modified form which continues to produce effects in the body ...
s such as 5α-dihydroprogesterone and allopregnanolone, acts indirectly as a
positive allosteric modulator In pharmacology and biochemistry, allosteric modulators are a group of substances that bind to a receptor to change that receptor's response to stimulus. Some of them, like benzodiazepines, are drugs. The site that an allosteric modulator binds to ...
of the GABAA receptor. Progesterone and some of its metabolites, such as 5β-dihydroprogesterone, are agonists of the
pregnane X receptor In the field of molecular biology, the pregnane X receptor (PXR), also known as the steroid and xenobiotic sensing nuclear receptor (SXR) or nuclear receptor subfamily 1, group I, member 2 (NR1I2) is a protein that in humans is encoded by the ' ...
(PXR), albeit weakly so ( EC50 >10 μM). In accordance, progesterone induces several
hepatic The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it is ...
cytochrome P450 Cytochromes P450 (CYPs) are a superfamily of enzymes containing heme as a cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various co ...
enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...
s, such as
CYP3A4 Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine. It oxidizes small foreign organic molecules (xenobiotics), such as toxins or drugs, so that they can be removed from t ...
, especially during
pregnancy Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ca ...
when concentrations are much higher than usual. Perimenopausal women have been found to have greater CYP3A4 activity relative to men and postmenopausal women, and it has been inferred that this may be due to the higher progesterone levels present in perimenopausal women. Progesterone modulates the activity of
CatSper The cation channels of sperm also known as Catsper channels or CatSper, are ion channels that are related to the two-pore channels and distantly related to TRP channels. The four members of this family form voltage-gated Ca2+ channels tha ...
(cation channels of sperm)
voltage-gated Voltage-gated ion channels are a class of transmembrane proteins that form ion channels that are activated by changes in the electrical membrane potential near the channel. The membrane potential alters the conformation of the channel proteins ...
Ca2+ channels. Since eggs release progesterone, sperm may use progesterone as a homing signal to swim toward eggs ( chemotaxis). As a result, it has been suggested that substances that block the progesterone binding site on CatSper channels could potentially be used in
male contraception Male contraceptives, also known as male birth control, are methods of preventing pregnancy that solely involve the male physiology. The most common kinds of male contraception include condoms, outercourse, and vasectomy. In domestic animals, ca ...
.


Biological function


Hormonal interactions

Progesterone has a number of physiological effects that are amplified in the presence of
estrogen Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal acti ...
s. Estrogens through
estrogen receptor Estrogen receptors (ERs) are a group of proteins found inside cells. They are receptors that are activated by the hormone estrogen (17β-estradiol). Two classes of ER exist: nuclear estrogen receptors ( ERα and ERβ), which are members of the ...
s (ERs) induce or
upregulate In the biological context of organisms' production of gene products, downregulation is the process by which a cell decreases the quantity of a cellular component, such as RNA or protein, in response to an external stimulus. The complementary pro ...
the
expression Expression may refer to: Linguistics * Expression (linguistics), a word, phrase, or sentence * Fixed expression, a form of words with a specific meaning * Idiom, a type of fixed expression * Metaphorical expression, a particular word, phrase, o ...
of the PR. One example of this is in
breast The breast is one of two prominences located on the upper ventral region of a primate's torso. Both females and males develop breasts from the same embryological tissues. In females, it serves as the mammary gland, which produces and sec ...
tissue, where estrogens allow progesterone to mediate lobuloalveolar development. Elevated levels of progesterone potently reduce the sodium-retaining activity of aldosterone, resulting in natriuresis and a reduction in extracellular fluid volume. Progesterone withdrawal, on the other hand, is associated with a temporary increase in sodium retention (reduced natriuresis, with an increase in extracellular fluid volume) due to the compensatory increase in aldosterone production, which combats the blockade of the mineralocorticoid receptor by the previously elevated level of progesterone.


Reproductive system

Progesterone has key effects via non-genomic signalling on human sperm as they migrate through the female tract before
fertilization Fertilisation or fertilization (see spelling differences), also known as generative fertilisation, syngamy and impregnation, is the fusion of gametes to give rise to a new individual organism or offspring and initiate its development. Proce ...
occurs, though the receptor(s) as yet remain unidentified. Detailed characterisation of the events occurring in sperm in response to progesterone has elucidated certain events including intracellular calcium transients and maintained changes, slow calcium oscillations, now thought to possibly regulate motility. It is produced by the ovaries. Progesterone has also been shown to demonstrate effects on octopus spermatozoa. Progesterone is sometimes called the "hormone of
pregnancy Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ca ...
", and it has many roles relating to the development of the fetus: * Progesterone converts the endometrium to its secretory stage to prepare the uterus for implantation. At the same time progesterone affects the
vaginal epithelium The vaginal epithelium is the inner lining of the vagina consisting of multiple layers of (squamous) cells. The basal membrane provides the support for the first layer of the epithelium-the basal layer. The intermediate layers lie upon the basal ...
and cervical mucus, making it thick and impenetrable to
sperm Sperm is the male reproductive cell, or gamete, in anisogamous forms of sexual reproduction (forms in which there is a larger, female reproductive cell and a smaller, male one). Animals produce motile sperm with a tail known as a flagellum, whi ...
. Progesterone is anti-
mitogenic A mitogen is a small bioactive protein or peptide that induces a cell to begin cell division, or enhances the rate of division (mitosis). Mitogenesis is the induction (triggering) of mitosis, typically via a mitogen. The mechanism of action of a ...
in endometrial epithelial cells, and as such, mitigates the tropic effects of
estrogen Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal acti ...
. If pregnancy does not occur, progesterone levels will decrease, leading, in the woman, to
menstruate Menstruation (also known as a period, among other colloquial terms) is the regular discharge of blood and mucosal tissue from the inner lining of the uterus through the vagina. The menstrual cycle is characterized by the rise and fall of h ...
. Normal menstrual bleeding is progesterone-withdrawal bleeding. If ovulation does not occur and the corpus luteum does not develop, levels of progesterone may be low, leading to anovulatory dysfunctional uterine bleeding. * During implantation and
gestation Gestation is the period of development during the carrying of an embryo, and later fetus, inside viviparous animals (the embryo develops within the parent). It is typical for mammals, but also occurs for some non-mammals. Mammals during pregna ...
, progesterone appears to decrease the maternal
immune In biology, immunity is the capability of multicellular organisms to resist harmful microorganisms. Immunity involves both specific and nonspecific components. The nonspecific components act as barriers or eliminators of a wide range of pathogens ...
response to allow for the acceptance of the pregnancy. * Progesterone decreases contractility of the uterine smooth muscle. This effect contributes to prevention of
preterm labor Preterm birth, also known as premature birth, is the birth of a baby at fewer than 37 weeks gestational age, as opposed to full-term delivery at approximately 40 weeks. Extreme preterm is less than 28 weeks, very early preterm birth is between ...
. * A drop in progesterone levels is possibly one step that facilitates the onset of
labor Labour or labor may refer to: * Childbirth, the delivery of a baby * Labour (human activity), or work ** Manual labour, physical work ** Wage labour, a socioeconomic relationship between a worker and an employer ** Organized labour and the la ...
. *In addition, progesterone inhibits
lactation Lactation describes the secretion of milk from the mammary glands and the period of time that a mother lactates to feed her young. The process naturally occurs with all sexually mature female mammals, although it may predate mammals. The proces ...
during pregnancy. The fall in progesterone levels following delivery is one of the triggers for milk production. The
fetus A fetus or foetus (; plural fetuses, feti, foetuses, or foeti) is the unborn offspring that develops from an animal embryo. Following embryonic development the fetal stage of development takes place. In human prenatal development, fetal deve ...
metabolize Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...
s placental progesterone in the production of
adrenal The adrenal glands (also known as suprarenal glands) are endocrine glands that produce a variety of hormones including adrenaline and the steroids aldosterone and cortisol. They are found above the kidneys. Each gland has an outer cortex whic ...
steroids.


Breasts


Lobuloalveolar development

Progesterone plays an important role in
breast development Breast development, also known as mammogenesis, is a complex biological process in primates that takes place throughout a female's life. It occurs across several phases, including prenatal development, puberty, and pregnancy. At menopause, bre ...
in women. In conjunction with
prolactin Prolactin (PRL), also known as lactotropin, is a protein best known for its role in enabling mammals to produce milk. It is influential in over 300 separate processes in various vertebrates, including humans. Prolactin is secreted from the pit ...
, it mediates lobuloalveolar maturation of the
mammary gland A mammary gland is an exocrine gland in humans and other mammals that produces milk to feed young offspring. Mammals get their name from the Latin word ''mamma'', "breast". The mammary glands are arranged in organs such as the breasts in pri ...
s during pregnancy to allow for
milk production A dairy is a business enterprise established for the harvesting or processing (or both) of animal milk – mostly from cows or buffaloes, but also from goats, sheep, horses, or camels – for human consumption. A dairy is typically located on ...
and thus
lactation Lactation describes the secretion of milk from the mammary glands and the period of time that a mother lactates to feed her young. The process naturally occurs with all sexually mature female mammals, although it may predate mammals. The proces ...
and
breastfeeding Breastfeeding, or nursing, is the process by which human breast milk is fed to a child. Breast milk may be from the breast, or may be expressed by hand or pumped and fed to the infant. The World Health Organization (WHO) recommends that br ...
of
offspring In biology, offspring are the young creation of living organisms, produced either by a single organism or, in the case of sexual reproduction, two organisms. Collective offspring may be known as a brood or progeny in a more general way. This ca ...
following
parturition Birth is the act or process of bearing or bringing forth offspring, also referred to in technical contexts as parturition. In mammals, the process is initiated by hormones which cause the muscular walls of the uterus to contract, expelling the f ...
(childbirth).
Estrogen Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal acti ...
induces expression of the PR in breast tissue and hence progesterone is dependent on estrogen to mediate lobuloalveolar development. It has been found that is a critical downstream mediator of progesterone-induced lobuloalveolar maturation. RANKL knockout mice show an almost identical mammary phenotype to PR knockout mice, including normal mammary ductal development but complete failure of the development of lobuloalveolar structures.


Ductal development

Though to a far lesser extent than estrogen, which is the major mediator of mammary ductal development (via the
ERα Estrogen receptor alpha (ERα), also known as NR3A1 (nuclear receptor subfamily 3, group A, member 1), is one of two main types of estrogen receptor, a nuclear receptor (mainly found as a chromatin-binding protein) that is activated by the sex ...
), progesterone may be involved in ductal development of the mammary glands to some extent as well. PR knockout mice or mice treated with the PR antagonist
mifepristone Mifepristone, also known as RU-486, is a medication typically used in combination with misoprostol to bring about a medical abortion during pregnancy and manage early miscarriage. This combination is 97% effective during the first 63 days of p ...
show delayed although otherwise normal mammary ductal development at puberty. In addition, mice modified to have overexpression of PRA display ductal hyperplasia, and progesterone induces ductal growth in the mouse mammary gland. Progesterone mediates ductal development mainly via induction of the
expression Expression may refer to: Linguistics * Expression (linguistics), a word, phrase, or sentence * Fixed expression, a form of words with a specific meaning * Idiom, a type of fixed expression * Metaphorical expression, a particular word, phrase, o ...
of amphiregulin, the same
growth factor A growth factor is a naturally occurring substance capable of stimulating cell proliferation, wound healing, and occasionally cellular differentiation. Usually it is a secreted protein or a steroid hormone. Growth factors are important for regul ...
that estrogen primarily induces the expression of to mediate ductal development. These animal findings suggest that, while not essential for full mammary ductal development, progesterone seems to play a potentiating or accelerating role in estrogen-mediated mammary ductal development.


Breast cancer risk

Progesterone also appears to be involved in the pathophysiology of
breast cancer Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or a re ...
, though its role, and whether it is a promoter or inhibitor of breast cancer risk, has not been fully elucidated. Most progestins, or synthetic progestogens, like
medroxyprogesterone acetate Medroxyprogesterone acetate (MPA), also known as depot medroxyprogesterone acetate (DMPA) in injectable form and sold under the brand name Depo-Provera among others, is a hormonal medication of the progestin type. It is used as a method of bi ...
, have been found to increase the risk of breast cancer in postmenopausal women in combination with estrogen as a component of
menopausal hormone therapy Hormone replacement therapy (HRT), also known as menopausal hormone therapy or postmenopausal hormone therapy, is a form of hormone therapy used to treat symptoms associated with female menopause. These symptoms can include hot flashes, vagina ...
. The combination of natural oral progesterone or the atypical progestin
dydrogesterone Dydrogesterone, sold under the brand name Duphaston & Dydroboon among others, is a progestin medication which is used for a variety of indications, including threatened or recurrent miscarriage during pregnancy, dysfunctional bleeding, infertil ...
with estrogen has been associated with less risk of breast cancer than progestins plus estrogen. However, this may simply be an artifact of the low progesterone levels produced with oral progesterone. More research is needed on the role of progesterone in breast cancer.


Skin health

The
estrogen receptor Estrogen receptors (ERs) are a group of proteins found inside cells. They are receptors that are activated by the hormone estrogen (17β-estradiol). Two classes of ER exist: nuclear estrogen receptors ( ERα and ERβ), which are members of the ...
, as well as the progesterone receptor, have been detected in the
skin Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other cuticle, animal coverings, such as the arthropod exoskeleton, have diffe ...
, including in
keratinocyte Keratinocytes are the primary type of cell found in the epidermis, the outermost layer of the skin. In humans, they constitute 90% of epidermal skin cells. Basal cells in the basal layer (''stratum basale'') of the skin are sometimes referre ...
s and fibroblasts. At
menopause Menopause, also known as the climacteric, is the time in women's lives when menstrual periods stop permanently, and they are no longer able to bear children. Menopause usually occurs between the age of 47 and 54. Medical professionals often ...
and thereafter, decreased levels of female
sex hormone Sex hormones, also known as sex steroids, gonadocorticoids and gonadal steroids, are steroid hormones that interact with vertebrate steroid hormone receptors. The sex hormones include the androgens, estrogens, and progestogens. Their effect ...
s result in atrophy, thinning, and increased wrinkling of the skin and a reduction in skin elasticity, firmness, and strength. These skin changes constitute an acceleration in
skin aging The human skin is the outer covering of the body and is the largest organ of the integumentary system. The skin has up to seven layers of ectodermal tissue guarding muscles, bones, ligaments and internal organs. Human skin is similar to ...
and are the result of decreased collagen content, irregularities in the
morphology Morphology, from the Greek and meaning "study of shape", may refer to: Disciplines * Morphology (archaeology), study of the shapes or forms of artifacts * Morphology (astronomy), study of the shape of astronomical objects such as nebulae, galaxies ...
of
epidermal The epidermis is the outermost of the three layers that comprise the skin, the inner layers being the dermis and hypodermis. The epidermis layer provides a barrier to infection from environmental pathogens and regulates the amount of water relea ...
skin cell Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other animal coverings, such as the arthropod exoskeleton, have different de ...
s, decreased
ground substance Ground substance is an amorphous gel-like substance in the extracellular space that contains all components of the extracellular matrix (ECM) except for fibrous materials such as collagen and elastin. Ground substance is active in the development, m ...
between
skin fiber Bast fibre (also called phloem fibre or skin fibre) is plant fibre collected from the phloem (the "inner bark", sometimes called "skin") or bast surrounding the stem of certain dicotyledonous plants. It supports the conductive cells of the phloe ...
s, and reduced
capillaries A capillary is a small blood vessel from 5 to 10 micrometres (μm) in diameter. Capillaries are composed of only the tunica intima, consisting of a thin wall of simple squamous endothelial cells. They are the smallest blood vessels in the body: ...
and
blood flow Hemodynamics or haemodynamics are the dynamics of blood flow. The circulatory system is controlled by homeostatic mechanisms of autoregulation, just as hydraulic circuits are controlled by control systems. The hemodynamic response continuously m ...
. The skin also becomes more dry during menopause, which is due to reduced skin
hydration Hydration may refer to: * Hydrate, a substance that contains water * Hydration enthalpy, energy released through hydrating a substance * Hydration reaction, a chemical addition reaction where a hydroxyl group and proton are added to a compound * ...
and surface lipids (sebum production). Along with chronological aging and photoaging, estrogen deficiency in menopause is one of the three main factors that predominantly influences skin aging. Hormone replacement therapy, consisting of systemic treatment with estrogen alone or in combination with a progestogen, has well-documented and considerable beneficial effects on the skin of postmenopausal women. These benefits include increased skin collagen content, skin thickness and elasticity, and skin hydration and surface lipids. Topical estrogen has been found to have similar beneficial effects on the skin. In addition, a study has found that topical 2% progesterone cream significantly increases skin elasticity and firmness and observably decreases wrinkles in peri- and postmenopausal women. Skin hydration and surface lipids, on the other hand, did not significantly change with topical progesterone. These findings suggest that progesterone, like estrogen, also has beneficial effects on the skin, and may be independently protective against skin aging.


Sexuality


Libido

Progesterone and its neurosteroid
active metabolite An active metabolite is an active form of a drug after it has been processed by the body. Metabolites of drugs An active metabolite results when a drug is metabolized by the body into a modified form which continues to produce effects in the body ...
allopregnanolone appear to be importantly involved in
libido Libido (; colloquial: sex drive) is a person's overall sexual drive or desire for sexual activity. Libido is influenced by biological, psychological, and social factors. Biologically, the sex hormones and associated neurotransmitters that act u ...
in females.


Homosexuality

Dr. Diana Fleischman, of the
University of Portsmouth The University of Portsmouth is a public university in Portsmouth, England. It is one of only four universities in the South East England, South East of England rated as Gold in the Government's Teaching Excellence Framework. With approximately 28 ...
, and colleagues looked for a relationship between progesterone and sexual attitudes in 92 women. Their research, published in the
Archives of Sexual Behavior The ''Archives of Sexual Behavior'' is a peer-reviewed academic journal in sexology. It is the official publication of the International Academy of Sex Research. History The journal was established in 1971 by Richard Green, who served as its e ...
found that women who had higher levels of progesterone scored higher on a questionnaire measuring homoerotic motivation. They also found that men who had high levels of progesterone were more likely to have higher homoerotic motivation scores after affiliative priming compared to men with low levels of progesterone.


Nervous system

Progesterone, like
pregnenolone Pregnenolone (P5), or pregn-5-en-3β-ol-20-one, is an endogenous steroid and precursor/ metabolic intermediate in the biosynthesis of most of the steroid hormones, including the progestogens, androgens, estrogens, glucocorticoids, and mineraloc ...
and
dehydroepiandrosterone Dehydroepiandrosterone (DHEA), also known as androstenolone, is an endogenous steroid hormone precursor. It is one of the most abundant circulating steroids in humans. DHEA is produced in the adrenal glands, the gonads, and the brain. It fun ...
(DHEA), belongs to an important group of endogenous steroids called neurosteroids. It can be metabolized within all parts of the
central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all par ...
. Neurosteroids are
neuromodulator Neuromodulation is the physiological process by which a given neuron uses one or more chemicals to regulate diverse populations of neurons. Neuromodulators typically bind to metabotropic, G-protein coupled receptors (GPCRs) to initiate a second ...
s, and are
neuroprotective Neuroprotection refers to the relative preservation of neuronal structure and/or function. In the case of an ongoing insult (a neurodegenerative insult) the relative preservation of neuronal integrity implies a reduction in the rate of neuronal los ...
,
neurogenic In biology, the nervous system is the highly complex part of an animal that coordinates its actions and sensory information by transmitting signals to and from different parts of its body. The nervous system detects environmental changes ...
, and regulate
neurotransmission Neurotransmission (Latin: ''transmissio'' "passage, crossing" from ''transmittere'' "send, let through") is the process by which signaling molecules called neurotransmitters are released by the axon terminal of a neuron (the presynaptic neuron), ...
and
myelin Myelin is a lipid-rich material that surrounds nerve cell axons (the nervous system's "wires") to insulate them and increase the rate at which electrical impulses (called action potentials) are passed along the axon. The myelinated axon can be ...
ation. The effects of progesterone as a neurosteroid are mediated predominantly through its interactions with non-nuclear PRs, namely the mPRs and PGRMC1, as well as certain other receptors, such as the σ1 and nACh receptors.


Brain damage

Previous studies have shown that progesterone supports the normal development of neurons in the brain, and that the hormone has a protective effect on damaged brain tissue. It has been observed in animal models that females have reduced susceptibility to
traumatic brain injury A traumatic brain injury (TBI), also known as an intracranial injury, is an injury to the brain caused by an external force. TBI can be classified based on severity (ranging from mild traumatic brain injury TBI/concussionto severe traumatic b ...
and this protective effect has been hypothesized to be caused by increased circulating levels of
estrogen Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal acti ...
and progesterone in females.


Proposed mechanism

The mechanism of progesterone protective effects may be the reduction of inflammation that follows brain trauma and hemorrhage. Damage incurred by traumatic brain injury is believed to be caused in part by mass
depolarization In biology, depolarization or hypopolarization is a change within a cell, during which the cell undergoes a shift in electric charge distribution, resulting in less negative charge inside the cell compared to the outside. Depolarization is ess ...
leading to
excitotoxicity In excitotoxicity, nerve cells suffer damage or death when the levels of otherwise necessary and safe neurotransmitters such as glutamate become pathologically high, resulting in excessive stimulation of receptors. For example, when glutamate ...
. One way in which progesterone helps to alleviate some of this excitotoxicity is by blocking the
voltage-dependent calcium channel Voltage-gated calcium channels (VGCCs), also known as voltage-dependent calcium channels (VDCCs), are a group of voltage-gated ion channels found in the membrane of excitable cells (''e.g.'', muscle, glial cells, neurons, etc.) with a permea ...
s that trigger neurotransmitter release. It does so by manipulating the signaling pathways of
transcription factor In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The fu ...
s involved in this release. Another method for reducing the excitotoxicity is by up-regulating the GABAA, a widespread inhibitory neurotransmitter receptor. Progesterone has also been shown to prevent
apoptosis Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...
in neurons, a common consequence of brain injury. It does so by inhibiting enzymes involved in the apoptosis pathway specifically concerning the mitochondria, such as activated
caspase 3 Caspase-3 is a caspase protein that interacts with caspase-8 and caspase-9. It is encoded by the ''CASP3'' gene. ''CASP3'' orthologs have been identified in numerous mammals for which complete genome data are available. Unique orthologs are als ...
and
cytochrome c The cytochrome complex, or cyt ''c'', is a small hemeprotein found loosely associated with the inner membrane of the mitochondrion. It belongs to the cytochrome c family of proteins and plays a major role in cell apoptosis. Cytochrome c is hig ...
. Not only does progesterone help prevent further damage, it has also been shown to aid in
neuroregeneration Neuroregeneration refers to the regrowth or repair of nervous tissues, cells or cell products. Such mechanisms may include generation of new neurons, glia, axons, myelin, or synapses. Neuroregeneration differs between the peripheral nervous system ...
. One of the serious effects of traumatic brain injury includes edema. Animal studies show that progesterone treatment leads to a decrease in edema levels by increasing the concentration of
macrophage Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer cel ...
s and microglia sent to the injured tissue. This was observed in the form of reduced leakage from the
blood brain barrier Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in the c ...
in secondary recovery in progesterone treated rats. In addition, progesterone was observed to have
antioxidant Antioxidants are compounds that inhibit oxidation, a chemical reaction that can produce free radicals. This can lead to polymerization and other chain reactions. They are frequently added to industrial products, such as fuels and lubricant ...
properties, reducing the concentration of
oxygen free radicals In chemistry, a radical, also known as a free radical, is an atom, molecule, or ion that has at least one unpaired electron, unpaired valence electron. With some exceptions, these unpaired electrons make radicals highly chemical reaction, chemi ...
faster than without. There is also evidence that the addition of progesterone can also help re
myelin Myelin is a lipid-rich material that surrounds nerve cell axons (the nervous system's "wires") to insulate them and increase the rate at which electrical impulses (called action potentials) are passed along the axon. The myelinated axon can be ...
ate damaged axons due to trauma, restoring some lost neural signal conduction. Another way progesterone aids in regeneration includes increasing the circulation of endothelial progenitor cells in the brain. This helps new
vasculature The blood circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the entire body of a human or other vertebrate. It includes the cardiovascular system, or vascular system, tha ...
to grow around scar tissue which helps repair the area of insult.


Addiction

Progesterone enhances the function of serotonin receptors in the brain, so an excess or deficit of progesterone has the potential to result in significant neurochemical issues. This provides an explanation for why some people resort to substances that enhance serotonin activity such as
nicotine Nicotine is a natural product, naturally produced alkaloid in the nightshade family of plants (most predominantly in tobacco and ''Duboisia hopwoodii'') and is widely used recreational drug use, recreationally as a stimulant and anxiolytic. As ...
, alcohol, and
cannabis ''Cannabis'' () is a genus of flowering plants in the family Cannabaceae. The number of species within the genus is disputed. Three species may be recognized: ''Cannabis sativa'', '' C. indica'', and '' C. ruderalis''. Alternatively ...
when their progesterone levels fall below optimal levels. * Sex differences in hormone levels may induce women to respond differently than men to nicotine. When women undergo cyclic changes or different hormonal transition phases (menopause, pregnancy, adolescence), there are changes in their progesterone levels. Therefore, females have an increased biological vulnerability to nicotine's reinforcing effects compared to males and progesterone may be used to counter this enhanced vulnerability. This information supports the idea that progesterone can affect behavior. * Similar to nicotine, cocaine also increases the release of dopamine in the brain. The neurotransmitter is involved in the reward center and is one of the main neurotransmitters involved with substance abuse and reliance. In a study of cocaine users, it was reported that progesterone reduced craving and the feeling of being stimulated by cocaine. Thus, progesterone was suggested as an agent that decreases cocaine craving by reducing the dopaminergic properties of the drug.


Societal

In a 2012 University of Amsterdam study of 120 women, women's luteal phase (higher levels of progesterone, and increasing levels of estrogen) was correlated with lower level of competitive behavior in gambling and math contest scenarios, while their premenstrual phase (sharply-decreasing levels of progesterone, and decreasing levels of estrogen) was correlated with a higher level of competitive behavior.


Other effects

* Progesterone also has a role in skin elasticity and bone strength, in
respiration Respiration may refer to: Biology * Cellular respiration, the process in which nutrients are converted into useful energy in a cell ** Anaerobic respiration, cellular respiration without oxygen ** Maintenance respiration, the amount of cellul ...
, in nerve tissue and in
female sexuality Human female sexuality encompasses a broad range of behaviors and processes, including female sexual identity and Human sexual activity, sexual behavior, the physiological, psychological, social, cultural, political, and spiritual or religious ...
, and the presence of progesterone receptors in certain muscle and fat tissue may hint at a role in
sexually dimorphic Sexual dimorphism is the condition where the sexes of the same animal and/or plant species exhibit different morphological characteristics, particularly characteristics not directly involved in reproduction. The condition occurs in most ani ...
proportions of those. * During pregnancy, progesterone is said to decrease uterine irritability. * During pregnancy, progesterone helps to suppress immune responses of the mother to fetal antigens, which prevents rejection of the fetus. * Progesterone raises epidermal growth factor-1 (EGF-1) levels, a factor often used to induce proliferation, and used to sustain cultures, of
stem cell In multicellular organisms, stem cells are undifferentiated or partially differentiated cells that can differentiate into various types of cells and proliferate indefinitely to produce more of the same stem cell. They are the earliest type o ...
s. * Progesterone increases core temperature (thermogenic function) during ovulation. * Progesterone reduces
spasm A spasm is a sudden involuntary contraction of a muscle, a group of muscles, or a hollow organ such as the bladder. A spasmodic muscle contraction may be caused by many medical conditions, including dystonia. Most commonly, it is a muscle c ...
and relaxes smooth muscle.
Bronchi A bronchus is a passage or airway in the lower respiratory tract that conducts air into the lungs. The first or primary bronchi pronounced (BRAN-KAI) to branch from the trachea at the carina are the right main bronchus and the left main bronchus. ...
are widened and
mucus Mucus ( ) is a slippery aqueous secretion produced by, and covering, mucous membranes. It is typically produced from cells found in mucous glands, although it may also originate from mixed glands, which contain both serous and mucous cells. It ...
regulated. (PRs are widely present in submucosal tissue.) * Progesterone acts as an
antiinflammatory Anti-inflammatory is the property of a substance or treatment that reduces inflammation or swelling. Anti-inflammatory drugs, also called anti-inflammatories, make up about half of analgesics. These drugs remedy pain by reducing inflammation as ...
agent and regulates the
immune response An immune response is a reaction which occurs within an organism for the purpose of defending against foreign invaders. These invaders include a wide variety of different microorganisms including viruses, bacteria, parasites, and fungi which could ...
. * Progesterone reduces
gall-bladder In vertebrates, the gallbladder, also known as the cholecyst, is a small hollow organ where bile is stored and concentrated before it is released into the small intestine. In humans, the pear-shaped gallbladder lies beneath the liver, although ...
activity. * Progesterone normalizes
blood Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in the c ...
clotting and vascular tone,
zinc Zinc is a chemical element with the symbol Zn and atomic number 30. Zinc is a slightly brittle metal at room temperature and has a shiny-greyish appearance when oxidation is removed. It is the first element in group 12 (IIB) of the periodi ...
and
copper Copper is a chemical element with the symbol Cu (from la, cuprum) and atomic number 29. It is a soft, malleable, and ductile metal with very high thermal and electrical conductivity. A freshly exposed surface of pure copper has a pinkis ...
levels,
cell Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Locations * Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery ...
oxygen Oxygen is the chemical element with the symbol O and atomic number 8. It is a member of the chalcogen group in the periodic table, a highly reactive nonmetal, and an oxidizing agent that readily forms oxides with most elements as wel ...
levels, and use of fat stores for energy. * Progesterone may affect gum health, increasing risk of gingivitis (gum inflammation). * Progesterone appears to prevent endometrial cancer (involving the uterine lining) by regulating the effects of estrogen. * Progesterone plays an important role in the signaling of insulin release and pancreatic function, and may affect the susceptibility to diabetes or gestational diabetes.


Biochemistry


Biosynthesis

In mammals, progesterone, like all other steroid
hormone A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and behavior. Hormones are required ...
s, is synthesized from
pregnenolone Pregnenolone (P5), or pregn-5-en-3β-ol-20-one, is an endogenous steroid and precursor/ metabolic intermediate in the biosynthesis of most of the steroid hormones, including the progestogens, androgens, estrogens, glucocorticoids, and mineraloc ...
, which itself is derived from
cholesterol Cholesterol is any of a class of certain organic molecules called lipids. It is a sterol (or modified steroid), a type of lipid. Cholesterol is biosynthesized by all animal cells and is an essential structural component of animal cell mem ...
. Cholesterol undergoes double oxidation to produce 22''R''-hydroxycholesterol and then 20α,22''R''-dihydroxycholesterol. This vicinal diol is then further oxidized with loss of the side chain starting at position C22 to produce pregnenolone. This reaction is catalyzed by
cytochrome Cytochromes are redox-active proteins containing a heme, with a central Fe atom at its core, as a cofactor. They are involved in electron transport chain and redox catalysis. They are classified according to the type of heme and its mode of bi ...
P450scc Cholesterol side-chain cleavage enzyme is commonly referred to as P450scc, where "scc" is an acronym for side-chain cleavage. P450scc is a mitochondrial enzyme that catalyzes conversion of cholesterol to pregnenolone. This is the first reactio ...
. The conversion of pregnenolone to progesterone takes place in two steps. First, the 3β-
hydroxyl In chemistry, a hydroxy or hydroxyl group is a functional group with the chemical formula and composed of one oxygen atom covalently bonded to one hydrogen atom. In organic chemistry, alcohols and carboxylic acids contain one or more hydroxy ...
group is oxidized to a keto group and second, the
double bond In chemistry, a double bond is a covalent bond between two atoms involving four bonding electrons as opposed to two in a single bond. Double bonds occur most commonly between two carbon atoms, for example in alkenes. Many double bonds exist betwee ...
is moved to C4, from C5 through a keto/
enol In organic chemistry, alkenols (shortened to enols) are a type of reactive structure or intermediate in organic chemistry that is represented as an alkene ( olefin) with a hydroxyl group attached to one end of the alkene double bond (). The t ...
tautomer Tautomers () are structural isomers (constitutional isomers) of chemical compounds that readily interconvert. The chemical reaction interconverting the two is called tautomerization. This conversion commonly results from the relocation of a hyd ...
ization reaction. This reaction is catalyzed by 3β-hydroxysteroid dehydrogenase/δ5-4-isomerase. Progesterone in turn is the precursor of the mineralocorticoid aldosterone, and after conversion to 17α-hydroxyprogesterone, of cortisol and androstenedione. Androstenedione can be converted to
testosterone Testosterone is the primary sex hormone and anabolic steroid in males. In humans, testosterone plays a key role in the development of Male reproductive system, male reproductive tissues such as testes and prostate, as well as promoting secondar ...
,
estrone Estrone (E1), also spelled oestrone, is a steroid, a weak estrogen, and a minor female sex hormone. It is one of three major endogenous estrogens, the others being estradiol and estriol. Estrone, as well as the other estrogens, are synthesized ...
, and
estradiol Estradiol (E2), also spelled oestradiol, is an estrogen steroid hormone and the major female sex hormone. It is involved in the regulation of the estrous and menstrual female reproductive cycles. Estradiol is responsible for the development o ...
, highlighting the critical role of progesterone in testosterone synthesis. Pregnenolone and progesterone can also be synthesized by
yeast Yeasts are eukaryotic, single-celled microorganisms classified as members of the fungus kingdom. The first yeast originated hundreds of millions of years ago, and at least 1,500 species are currently recognized. They are estimated to constitut ...
. Approximately 25 mg of progesterone is secreted from the ovaries per day in women, while the adrenal glands produce about 2 mg of progesterone per day.


Distribution

Progesterone binds extensively to
plasma protein Blood-proteins, also termed plasma proteins, are proteins present in blood plasma. They serve many different functions, including transport of lipids, hormones, vitamins and minerals in activity and functioning of the immune system. Other blood pr ...
s, including
albumin Albumin is a family of globular proteins, the most common of which are the serum albumins. All the proteins of the albumin family are water-soluble, moderately soluble in concentrated salt solutions, and experience heat denaturation. Albumins ...
(50–54%) and
transcortin Transcortin, also known as corticosteroid-binding globulin (CBG) or serpin A6, is a protein produced in the liver in animals. In humans it is encoded by the SERPINA6 gene. It is an alpha-globulin. Function This gene encodes an alpha-globulin p ...
(43–48%). It has similar affinity for albumin relative to the PR.


Metabolism

The
metabolism Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...
of progesterone is rapid and extensive and occurs mainly in the
liver The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...
, though
enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...
s that metabolize progesterone are also expressed widely in the
brain A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a v ...
,
skin Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other cuticle, animal coverings, such as the arthropod exoskeleton, have diffe ...
, and various other extrahepatic tissues. Progesterone has an
elimination half-life Biological half-life (also known as elimination half-life, pharmacologic half-life) is the time taken for concentration of a biological substance (such as a medication) to decrease from its maximum concentration ( Cmax) to half of Cmax in the bl ...
of only approximately 5 minutes in circulation. The metabolism of progesterone is complex, and it may form as many as 35 different unconjugated
metabolite In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...
s when it is ingested orally. Progesterone is highly susceptible to enzymatic reduction via reductases and
hydroxysteroid dehydrogenase Hydroxysteroid dehydrogenases (HSDs) are a group of alcohol oxidoreductases that catalyze the dehydrogenation of hydroxysteroids. These enzymes also catalyze the reverse reaction, acting as ketosteroid reductases (KSRs). There are four types, cl ...
s due to its
double bond In chemistry, a double bond is a covalent bond between two atoms involving four bonding electrons as opposed to two in a single bond. Double bonds occur most commonly between two carbon atoms, for example in alkenes. Many double bonds exist betwee ...
(between the C4 and C5 positions) and its two ketones (at the C3 and C20 positions). The major
metabolic pathway In biochemistry, a metabolic pathway is a linked series of chemical reactions occurring within a cell. The reactants, products, and intermediates of an enzymatic reaction are known as metabolites, which are modified by a sequence of chemical reac ...
of progesterone is reduction by 5α-reductase and 5β-reductase into the dihydrogenated 5α-dihydroprogesterone and 5β-dihydroprogesterone, respectively. This is followed by the further reduction of these metabolites via 3α-hydroxysteroid dehydrogenase and 3β-hydroxysteroid dehydrogenase into the tetrahydrogenated allopregnanolone, pregnanolone, isopregnanolone, and epipregnanolone. Subsequently,
20α-hydroxysteroid dehydrogenase In enzymology, a 20-α-hydroxysteroid dehydrogenase () is an enzyme that catalyzes the chemical reaction :17alpha,20alpha-dihydroxypregn-4-en-3-one + NAD(P)+ \rightleftharpoons 17alpha-hydroxyprogesterone + NAD(P)H + H+ The 3 substrates of th ...
and 20β-hydroxysteroid dehydrogenase reduce these metabolites to form the corresponding hexahydrogenated pregnanediols (eight different
isomer In chemistry, isomers are molecules or polyatomic ions with identical molecular formulae – that is, same number of atoms of each element – but distinct arrangements of atoms in space. Isomerism is existence or possibility of isomers. Iso ...
s in total), which are then conjugated via
glucuronidation Glucuronidation is often involved in drug metabolism of substances such as drugs, pollutants, bilirubin, androgens, estrogens, mineralocorticoids, glucocorticoids, fatty acid derivatives, retinoids, and bile acids. These linkages involve gl ...
and/or
sulfation Sulfation is the chemical reaction that entails the addition of SO3 group. In principle, many sulfations would involve reactions of sulfur trioxide (SO3). In practice, most sulfations are effected less directly. Regardless of the mechanism, the ...
, released from the liver into circulation, and
excreted Excretion is a process in which metabolic waste is eliminated from an organism. In vertebrates this is primarily carried out by the lungs, kidneys, and skin. This is in contrast with secretion, where the substance may have specific tasks after lea ...
by the
kidney The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blood ...
s into the
urine Urine is a liquid by-product of metabolism in humans and in many other animals. Urine flows from the kidneys through the ureters to the urinary bladder. Urination results in urine being excreted from the body through the urethra. Cellular ...
. The major metabolite of progesterone in the urine is the 3α,5β,20α isomer of
pregnanediol glucuronide Pregnanediol glucuronide, or 5β-pregnane-3α,20α-diol 3α-glucuronide, is the major metabolite of progesterone and the C3α glucuronide conjugate of pregnanediol (5β-pregnane-3α,20α-diol). Approximately 15 to 30% of a parenteral dose of ...
, which has been found to constitute 15 to 30% of an injection of progesterone. Other metabolites of progesterone formed by the enzymes in this pathway include 3α-dihydroprogesterone,
3β-dihydroprogesterone 3β-Dihydroprogesterone (3β-DHP), also known as 3β-hydroxyprogesterone, or pregn-4-en-3β-ol-20-one (4-pregnenolone, δ4-pregnenolone), is an endogenous steroid. It is biosynthesized by 3β-hydroxysteroid dehydrogenase from progesterone. Un ...
, 20α-dihydroprogesterone, and
20β-dihydroprogesterone 20β-Dihydroprogesterone (20β-DHP), also known as 20β-hydroxyprogesterone (20β-OHP), is an endogenous metabolite of progesterone which is formed by 20β-hydroxysteroid dehydrogenase (20β-HSD). It is a progestogen similarly to progesterone, ...
, as well as various combination products of the enzymes aside from those already mentioned. Progesterone can also first be
hydroxylated In chemistry, hydroxylation can refer to: *(i) most commonly, hydroxylation describes a chemistry, chemical process that introduces a hydroxyl group () into an organic compound. *(ii) the ''degree of hydroxylation'' refers to the number of OH gr ...
(see below) and then reduced. Endogenous progesterone is metabolized approximately 50% into 5α-dihydroprogesterone in the corpus luteum, 35% into 3β-dihydroprogesterone in the liver, and 10% into 20α-dihydroprogesterone. Relatively small portions of progesterone are
hydroxylated In chemistry, hydroxylation can refer to: *(i) most commonly, hydroxylation describes a chemistry, chemical process that introduces a hydroxyl group () into an organic compound. *(ii) the ''degree of hydroxylation'' refers to the number of OH gr ...
via 17α-hydroxylase (CYP17A1) and 21-hydroxylase (CYP21A2) into 17α-hydroxyprogesterone and
11-deoxycorticosterone 11-Deoxycorticosterone (DOC), or simply deoxycorticosterone, also known as 21-hydroxyprogesterone, as well as desoxycortone (INN), deoxycortone, and cortexone, is a steroid hormone produced by the adrenal gland that possesses mineralocorticoid ac ...
(21-hydroxyprogesterone), respectively, and pregnanetriols are formed secondarily to 17α-hydroxylation. Even smaller amounts of progesterone may be also hydroxylated via 11β-hydroxylase (CYP11B1) and to a lesser extent via
aldosterone synthase Aldosterone synthase, also called steroid 18-hydroxylase, corticosterone 18-monooxygenase or P450C18, is a steroid hydroxylase cytochrome P450 enzyme involved in the biosynthesis of the mineralocorticoid aldosterone and other steroids. The enzyme ...
(CYP11B2) into 11β-hydroxyprogesterone. In addition, progesterone can be hydroxylated in the liver by other
cytochrome P450 Cytochromes P450 (CYPs) are a superfamily of enzymes containing heme as a cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various co ...
enzymes which are not steroid-specific. 6β-Hydroxylation, which is catalyzed mainly by
CYP3A4 Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine. It oxidizes small foreign organic molecules (xenobiotics), such as toxins or drugs, so that they can be removed from t ...
, is the major transformation, and is responsible for approximately 70% of cytochrome P450-mediated progesterone metabolism. Other routes include 6α-, 16α-, and 16β-hydroxylation. However, treatment of women with ketoconazole, a strong CYP3A4 inhibitor, had minimal effects on progesterone levels, producing only a slight and non-significant increase, and this suggests that cytochrome P450 enzymes play only a small role in progesterone metabolism.


Levels

In women, progesterone levels are relatively low during the preovulatory phase of the
menstrual cycle The menstrual cycle is a series of natural changes in hormone production and the structures of the uterus and ovaries of the female reproductive system that make pregnancy possible. The ovarian cycle controls the production and release of eggs a ...
, rise after
ovulation Ovulation is the release of eggs from the ovaries. In women, this event occurs when the ovarian follicles rupture and release the secondary oocyte ovarian cells. After ovulation, during the luteal phase, the egg will be available to be fertilized ...
, and are elevated during the
luteal phase The corpus luteum (Latin for "yellow body"; plural corpora lutea) is a temporary endocrine structure in female ovaries involved in the production of relatively high levels of progesterone, and moderate levels of estradiol, and inhibin A. It is th ...
, as shown in the diagram above. Progesterone levels tend to be less than 2 ng/mL prior to ovulation and greater than 5 ng/mL after ovulation. If
pregnancy Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ca ...
occurs,
human chorionic gonadotropin Human chorionic gonadotropin (hCG) is a hormone for the maternal recognition of pregnancy produced by trophoblast cells that are surrounding a growing embryo (syncytiotrophoblast initially), which eventually forms the placenta after implantation ...
is released, maintaining the corpus luteum and allowing it to maintain levels of progesterone. Between 7 and 9 weeks, the placenta begins to produce progesterone in place of the corpus luteum in a process called the luteal-placental shift. After the luteal-placental shift, progesterone levels start to rise further and may reach 100 to 200 ng/mL at term. Whether a decrease in progesterone levels is critical for the initiation of
labor Labour or labor may refer to: * Childbirth, the delivery of a baby * Labour (human activity), or work ** Manual labour, physical work ** Wage labour, a socioeconomic relationship between a worker and an employer ** Organized labour and the la ...
has been argued and may be species-specific. After delivery of the placenta and during lactation, progesterone levels are very low. Progesterone levels are low in children and postmenopausal women. Adult males have levels similar to those in women during the follicular phase of the menstrual cycle.


Ranges

Blood test results should always be interpreted using the reference ranges provided by the laboratory that performed the results. Example reference ranges are listed below.


Sources


Animal

Progesterone is produced in high amounts in the
ovaries The ovary is an organ in the female reproductive system that produces an ovum. When released, this travels down the fallopian tube into the uterus, where it may become fertilized by a sperm. There is an ovary () found on each side of the body. T ...
(by the corpus luteum) from the onset of
puberty Puberty is the process of physical changes through which a child's body matures into an adult body capable of sexual reproduction. It is initiated by hormonal signals from the brain to the gonads: the ovaries in a girl, the testes in a boy. ...
to
menopause Menopause, also known as the climacteric, is the time in women's lives when menstrual periods stop permanently, and they are no longer able to bear children. Menopause usually occurs between the age of 47 and 54. Medical professionals often ...
, and is also produced in smaller amounts by the
adrenal gland The adrenal glands (also known as suprarenal glands) are endocrine glands that produce a variety of hormones including adrenaline and the steroids aldosterone and cortisol. They are found above the kidneys. Each gland has an outer cortex whic ...
s after the onset of
adrenarche Adrenarche is an early stage in sexual maturation that happens in some higher primates and in humans, typically peaks at around 20 years of age, and is involved in the development of pubic hair, body odor, skin oiliness, axillary hair, sexual ...
in both males and females. To a lesser extent, progesterone is produced in
nervous tissue Nervous tissue, also called neural tissue, is the main tissue component of the nervous system. The nervous system regulates and controls body functions and activity. It consists of two parts: the central nervous system (CNS) comprising the brain ...
, especially in the brain, and in adipose (fat) tissue, as well. During human
pregnancy Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ca ...
, progesterone is produced in increasingly high amounts by the ovaries and
placenta The placenta is a temporary embryonic and later fetal organ that begins developing from the blastocyst shortly after implantation. It plays critical roles in facilitating nutrient, gas and waste exchange between the physically separate mater ...
. At first, the source is the corpus luteum that has been "rescued" by the presence of
human chorionic gonadotropin Human chorionic gonadotropin (hCG) is a hormone for the maternal recognition of pregnancy produced by trophoblast cells that are surrounding a growing embryo (syncytiotrophoblast initially), which eventually forms the placenta after implantation ...
(hCG) from the conceptus. However, after the 8th week, production of progesterone shifts to the placenta. The placenta utilizes maternal cholesterol as the initial substrate, and most of the produced progesterone enters the maternal circulation, but some is picked up by the fetal circulation and used as substrate for fetal corticosteroids. At term the placenta produces about 250 mg progesterone per day. An additional animal source of progesterone is milk products. After consumption of milk products the level of bioavailable progesterone goes up.


Plants

In at least one plant, ''
Juglans regia ''Juglans regia'', the Persian walnut, English walnut, Carpathian walnut, Madeira walnut, or especially in Great Britain, common walnut, is an Old World walnut tree species native to the region stretching from the Balkans eastward to the Himala ...
'', progesterone has been detected. In addition, progesterone-like steroids are found in ''
Dioscorea mexicana ''Dioscorea mexicana'', Mexican yam or ''cabeza de negro'' is a species of yam in the genus ''Dioscorea''. ''Dioscorea mexicana'' is a caudiciform dioscorea having either a partly to completely above-ground dome-shaped caudex with a thick, ...
''. ''Dioscorea mexicana'' is a plant that is part of the yam family native to
Mexico Mexico (Spanish: México), officially the United Mexican States, is a country in the southern portion of North America. It is bordered to the north by the United States; to the south and west by the Pacific Ocean; to the southeast by Guatema ...
. It contains a steroid called diosgenin that is taken from the plant and is converted into progesterone. Diosgenin and progesterone are also found in other '' Dioscorea'' species, as well as in other plants that are not closely related, such as fenugreek. Another plant that contains substances readily convertible to progesterone is '' Dioscorea pseudojaponica'' native to
Taiwan Taiwan, officially the Republic of China (ROC), is a country in East Asia, at the junction of the East and South China Seas in the northwestern Pacific Ocean, with the People's Republic of China (PRC) to the northwest, Japan to the nort ...
. Research has shown that the Taiwanese yam contains saponins — steroids that can be converted to diosgenin and thence to progesterone. Many other ''Dioscorea'' species of the yam family contain steroidal substances from which progesterone can be produced. Among the more notable of these are ''
Dioscorea villosa ''Dioscorea villosa'' is a species of twining tuberous vine which is native to eastern North America. It is commonly known as wild yam, colic root, rheumatism root, devil's bones, and fourleaf yam,. It is common and widespread in a range stretchi ...
'' and '' Dioscorea polygonoides''. One study showed that the ''Dioscorea villosa'' contains 3.5% diosgenin. '' Dioscorea polygonoides'' has been found to contain 2.64% diosgenin as shown by
gas chromatography-mass spectrometry Gas is one of the four fundamental states of matter (the others being solid, liquid, and plasma). A pure gas may be made up of individual atoms (e.g. a noble gas like neon), elemental molecules made from one type of atom (e.g. oxygen), or ...
. Many of the ''Dioscorea'' species that originate from the yam family grow in countries that have tropical and subtropical climates.


Medical use

Progesterone is used as a
medication A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy (pharmacotherapy) is an important part of the medical field and re ...
. It is used in combination with
estrogen Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal acti ...
s mainly in hormone therapy for
menopausal Menopause, also known as the climacteric, is the time in women's lives when menstrual periods stop permanently, and they are no longer able to bear children. Menopause usually occurs between the age of 47 and 54. Medical professionals often ...
symptom Signs and symptoms are the observed or detectable signs, and experienced symptoms of an illness, injury, or condition. A sign for example may be a higher or lower temperature than normal, raised or lowered blood pressure or an abnormality showin ...
s and low sex hormone levels in women. It is also used in women to support
pregnancy Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ca ...
and
fertility Fertility is the capability to produce offspring through reproduction following the onset of sexual maturity. The fertility rate is the average number of children born by a female during her lifetime and is quantified demographically. Fertili ...
and to treat
gynecological disorder Gynaecology or gynecology (see spelling differences) is the area of medicine that involves the treatment of women's diseases, especially those of the reproductive organs. It is often paired with the field of obstetrics, forming the combined area ...
s. Progesterone has been shown to prevent miscarriage in women with 1) vaginal bleeding early in their current pregnancy and 2) a previous history of miscarriage. Progesterone can be taken
by mouth Oral administration is a route of administration where a substance is taken through the mouth. Per os abbreviated to P.O. is sometimes used as a direction for medication to be taken orally. Many medications are taken orally because they are i ...
, through the vagina, and by
injection Injection or injected may refer to: Science and technology * Injective function, a mathematical function mapping distinct arguments to distinct values * Injection (medicine), insertion of liquid into the body with a syringe * Injection, in broadca ...
into
muscle Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscl ...
or
fat In nutrition, biology, and chemistry, fat usually means any ester of fatty acids, or a mixture of such compounds, most commonly those that occur in living beings or in food. The term often refers specifically to triglycerides (triple est ...
, among other
route Route or routes may refer to: * Route (gridiron football), a path run by a wide receiver * route (command), a program used to configure the routing table * Route, County Antrim, an area in Northern Ireland * ''The Route'', a 2013 Ugandan film * Ro ...
s.


Chemistry

Progesterone is a
naturally occurring A natural product is a natural compound or substance produced by a living organism—that is, found in nature. In the broadest sense, natural products include any substance produced by life. Natural products can also be prepared by chemical sy ...
pregnane Pregnane, also known as 17β-ethylandrostane or as 10β,13β-dimethyl-17β-ethylgonane, is a C21 steroid and, indirectly, a parent of progesterone. It is a parent hydrocarbon for two series of steroids stemming from 5α-pregnane (originally allop ...
steroid and is also known as pregn-4-ene-3,20-dione. It has a
double bond In chemistry, a double bond is a covalent bond between two atoms involving four bonding electrons as opposed to two in a single bond. Double bonds occur most commonly between two carbon atoms, for example in alkenes. Many double bonds exist betwee ...
( 4-ene) between the C4 and C5 positions and two ketone
group A group is a number of persons or things that are located, gathered, or classed together. Groups of people * Cultural group, a group whose members share the same cultural identity * Ethnic group, a group whose members share the same ethnic ide ...
s (3,20- dione), one at the C3 position and the other at the C20 position.


Synthesis

Progesterone is commercially produced by semisynthesis. Two main routes are used: one from yam diosgenin first pioneered by Marker in 1940, and one based on soy
phytosterol Phytosterols are phytosteroids, similar to cholesterol, that serve as structural components of biological membranes of plants. They encompass plant sterols and stanols. More than 250 sterols and related compounds have been identified. Free phy ...
s scaled up in the 1970s. Additional (not necessarily economical) semisyntheses of progesterone have also been reported starting from a variety of steroids. For the example,
cortisone Cortisone is a pregnene (21-carbon) steroid hormone. It is a naturally-occurring corticosteroid metabolite that is also used as a pharmaceutical prodrug; it is not synthesized in the adrenal glands. Cortisol is converted by the action of the enz ...
can be simultaneously deoxygenated at the C-17 and C-21 position by treatment with iodotrimethylsilane in
chloroform Chloroform, or trichloromethane, is an organic compound with chemical formula, formula Carbon, CHydrogen, HChlorine, Cl3 and a common organic solvent. It is a colorless, strong-smelling, dense liquid produced on a large scale as a precursor to ...
to produce 11-keto-progesterone (ketogestin), which in turn can be reduced at position-11 to yield progesterone.


Marker semisynthesis

An economical
semisynthesis Semisynthesis, or partial chemical synthesis, is a type of chemical synthesis that uses chemical compounds isolated from natural sources (such as microbial cell cultures or plant material) as the starting materials to produce novel compounds with ...
of progesterone from the plant steroid diosgenin isolated from yams was developed by
Russell Marker Russell Earl Marker (March 12, 1902 – March 3, 1995) was an American chemist who invented the octane rating system when he was working at the Ethyl Corporation. Later in his career, he went on to found a steroid industry in Mexico when he s ...
in 1940 for the
Parke-Davis Parke-Davis is a subsidiary of the pharmaceutical company Pfizer. Although Parke, Davis & Co. is no longer an independent corporation, it was once America's oldest and largest drug maker, and played an important role in medical history. In 1970 ...
pharmaceutical company. This synthesis is known as the Marker degradation. The 16-DPA intermediate is important to the synthesis of many other medically important steroids. A very similar approach can produce 16-DPA from solanine.


Soy semisynthesis

Progesterone can also be made from the
stigmasterol Stigmasterol – a plant sterol (''phytosterol'') – is among the most abundant of plant sterols, having a major function to maintain the structure and physiology of cell membranes. In the European Union, it is a food additive listed with E num ...
found in
soybean oil Soybean oil (British English: soyabean oil) is a vegetable oil extracted from the seeds of the soybean (''Glycine max''). It is one of the most widely consumed cooking oils and the second most consumed vegetable oil. As a drying oil, processed s ...
also. c.f. Percy Julian.


Total synthesis

A
total synthesis Total synthesis is the complete chemical synthesis of a complex molecule, often a natural product, from simple, commercially-available precursors. It usually refers to a process not involving the aid of biological processes, which distinguishes i ...
of progesterone was reported in 1971 by W.S. Johnson. The synthesis begins with reacting the
phosphonium salt In polyatomic cations with the chemical formula (where R is a hydrogen or an alkyl, aryl, or halide group). These cations have tetrahedral structures. The salts are generally colorless or take the color of the anions. Types of phosphonium c ...
7 with
phenyl lithium Phenyllithium or lithobenzene is an organometallic agent with the empirical formula C6H5Li. It is most commonly used as a metalating agent in organic syntheses and a substitute for Grignard reagents for introducing phenyl groups in organic synth ...
to produce the phosphonium ylide 8. The ylide 8 is reacted with an
aldehyde In organic chemistry, an aldehyde () is an organic compound containing a functional group with the structure . The functional group itself (without the "R" side chain) can be referred to as an aldehyde but can also be classified as a formyl grou ...
to produce the
alkene In organic chemistry, an alkene is a hydrocarbon containing a carbon–carbon double bond. Alkene is often used as synonym of olefin, that is, any hydrocarbon containing one or more double bonds.H. Stephen Stoker (2015): General, Organic, an ...
9. The
ketal In organic chemistry, an acetal is a functional group with the connectivity . Here, the R groups can be organic fragments (a carbon atom, with arbitrary other atoms attached to that) or hydrogen, while the R' groups must be organic fragments no ...
protecting groups of 9 are hydrolyzed to produce the diketone 10, which in turn is cyclized to form the cyclopentenone 11. The ketone of 11 is reacted with methyl lithium to yield the tertiary alcohol 12, which in turn is treated with acid to produce the tertiary cation 13. The key step of the synthesis is the π-cation cyclization of 13 in which the B-, C-, and D-rings of the steroid are simultaneously formed to produce 14. This step resembles the cationic cyclization reaction used in the biosynthesis of steroids and hence is referred to as ''biomimetic''. In the next step the
enol In organic chemistry, alkenols (shortened to enols) are a type of reactive structure or intermediate in organic chemistry that is represented as an alkene ( olefin) with a hydroxyl group attached to one end of the alkene double bond (). The t ...
orthoester In organic chemistry, an ortho ester is a functional group containing three alkoxy groups attached to one carbon atom, i.e. with the general formula . Orthoesters may be considered as products of exhaustive alkylation of unstable orthocarboxylic ...
is hydrolyzed to produce the ketone 15. The cyclopentene A-ring is then opened by oxidizing with ozone to produce 16. Finally, the diketone 17 undergoes an intramolecular
aldol condensation An aldol condensation is a condensation reaction in organic chemistry in which two carbonyl moieties (of aldehydes or ketones) react to form a β-hydroxyaldehyde or β-hydroxyketone (an aldol reaction), and this is then followed by dehydration to ...
by treating with aqueous potassium hydroxide to produce progesterone.


History

George W. Corner and Willard M. Allen discovered the hormonal action of progesterone in 1929. By 1931–1932, nearly pure crystalline material of high progestational activity had been isolated from the corpus luteum of animals, and by 1934, pure crystalline progesterone had been refined and obtained and the
chemical structure A chemical structure determination includes a chemist's specifying the molecular geometry and, when feasible and necessary, the electronic structure of the target molecule or other solid. Molecular geometry refers to the spatial arrangement of at ...
of progesterone was determined. This was achieved by
Adolf Butenandt Adolf Friedrich Johann Butenandt (; 24 March 1903 – 18 January 1995) was a German biochemist. He was awarded the Nobel Prize in Chemistry in 1939 for his "work on sex hormones." He initially rejected the award in accordance with government po ...
at the ''Chemisches Institut'' of
Technical University An institute of technology (also referred to as: technological university, technical university, university of technology, technological educational institute, technical college, polytechnic university or just polytechnic) is an institution of te ...
in Danzig, who extracted this new compound from several thousand liters of
urine Urine is a liquid by-product of metabolism in humans and in many other animals. Urine flows from the kidneys through the ureters to the urinary bladder. Urination results in urine being excreted from the body through the urethra. Cellular ...
.
Chemical synthesis As a topic of chemistry, chemical synthesis (or combination) is the artificial execution of chemical reactions to obtain one or several products. This occurs by physical and chemical manipulations usually involving one or more reactions. In moder ...
of progesterone from
stigmasterol Stigmasterol – a plant sterol (''phytosterol'') – is among the most abundant of plant sterols, having a major function to maintain the structure and physiology of cell membranes. In the European Union, it is a food additive listed with E num ...
and pregnanediol was accomplished later that year. Up to this point, progesterone, known generically as corpus luteum hormone, had been being referred to by several groups by different names, including corporin, lutein, luteosterone, and progestin. In 1935, at the time of the Second International Conference on the Standardization of Sex Hormones in
London, England London is the capital and largest city of England and the United Kingdom, with a population of just under 9 million. It stands on the River Thames in south-east England at the head of a estuary down to the North Sea, and has been a major s ...
, a compromise was made between the groups and the name progesterone (progestational steroidal ketone) was created.


Veterinary use

The use of progesterone tests in dog breeding to pinpoint ovulation is becoming more widely used. There are several tests available but the most reliable test is a blood test with blood drawn by a veterinarian and sent to a lab for processing. Results can usually be obtained with 24 to 72 hours. The rationale for using progesterone tests is that increased numbers begin in close proximity to preovulatory surge in gonadotrophins and continue through ovulation and estrus. When progesterone levels reach certain levels they can signal the stage of estrus the female is. Prediction of birth date of the pending litter can be very accurate if ovulation date is known. Puppies deliver with a day or two of 9 weeks gestation in most cases. It is not possible to determine pregnancy using progesterone tests once a breeding has taken place, however. This is due to the fact that, in dogs, progesterone levels remain elevated throughout the estrus period.


References


External links


Progesterone MS Spectrum
* * {{Navboxes , title =
Biological activity In pharmacology, biological activity or pharmacological activity describes the beneficial or adverse effects of a drug on living matter. When a drug is a complex chemical mixture, this activity is exerted by the substance's active ingredient or ...
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