Progesterone
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Progesterone
Progesterone (P4) is an endogenous steroid and progestogen sex hormone involved in the menstrual cycle, pregnancy, 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 in the production of other endogenous steroids, including the sex hormones and the corticosteroids, 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 for contraception, to reduce the risk of uterine or cervical cancer, in hormone replacement therapy, and in feminizing hormone therapy. It was first prescribed in 1934. Biological activity Progesterone is the most important progestogen in the body. As a potent agonist of the nuclear progesterone receptor (nPR) ...
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Progestogen
Progestogens, also sometimes written progestagens or gestagens, are a class of natural or synthetic steroid hormones that bind to and activate the progesterone receptors (PR). Progesterone is the major and most important progestogen in the body. The progestogens are named for their function in maintaining pregnancy (i.e., ''progestational''), although they are also present at other phases of the estrous and menstrual cycles. The progestogens are one of three types of sex hormones, the others being estrogens like estradiol and androgens/anabolic steroids like testosterone. In addition, they are one of the five major classes of steroid hormones, the others being the androgens, estrogens, glucocorticoids, and mineralocorticoids, as well as the neurosteroids. All endogenous progestogens are characterized by their basic 21-carbon skeleton, called a pregnane skeleton (C21). In similar manner, the estrogens possess an estrane skeleton (C18), and androgens, an androstane skeleton (C19). ...
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Sex Hormone-binding Globulin
Sex hormone-binding globulin (SHBG) or sex steroid-binding globulin (SSBG) is a glycoprotein that binds to androgens and estrogens. When produced by the Sertoli cells in the seminiferous tubules of the testis, it has also been called androgen-binding protein (ABP). Other steroid hormones such as progesterone, cortisol, and other corticosteroids are bound by transcortin. SHBG is found in all vertebrates apart from birds. Function Testosterone and estradiol circulate in the bloodstream, loosely bound mostly to serum albumin (~54%), and to a lesser extent bound tightly to SHBG (~44%). Only a very small fraction of about 1 to 2% is unbound, or "free," and thus biologically active and able to enter a cell and activate its receptor. SHBG inhibits the function of these hormones. Thus, the local bioavailability of sex hormones is influenced by the level of SHBG. Because SHBGbinds to testosterone (T) and dihydrotestosterone (DHT), these hormones are made less lipophilic and become conc ...
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Steroid
A steroid is a biologically active organic compound with four rings arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes that alter membrane fluidity; and as signaling molecules. Hundreds of steroids are found in plants, animals and fungi. All steroids are manufactured in cells from the sterols lanosterol (opisthokonts) or cycloartenol (plants). Lanosterol and cycloartenol are derived from the cyclization of the triterpene squalene. The steroid core structure is typically composed of seventeen carbon atoms, bonded in four " fused" rings: three six-member cyclohexane rings (rings A, B and C in the first illustration) and one five-member cyclopentane ring (the D ring). Steroids vary by the functional groups attached to this four-ring core and by the oxidation state of the rings. Sterols are forms of steroids with a hydroxy group at position three and a skeleton derived from cholestane. ''A ...
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Neurosteroid
Neurosteroids, also known as neuroactive steroids, are endogenous or exogenous steroids that rapidly alter neuronal excitability through interaction with ligand-gated ion channels and other cell surface receptors. The term ''neurosteroid'' was coined by the French physiologist Étienne-Émile Baulieu and refers to steroids synthesized in the brain. The term, ''neuroactive steroid'' refers to steroids that can be synthesized in the brain, or are synthesized by an endocrine gland, that then reach the brain through the bloodstream and have effects on brain function. The term neuroactive steroids was first coined in 1992 by Steven Paul and Robert Purdy. In addition to their actions on neuronal membrane receptors, some of these steroids may also exert effects on gene expression via nuclear steroid hormone receptors. Neurosteroids have a wide range of potential clinical applications from sedation to treatment of epilepsy and traumatic brain injury. Ganaxolone, a synthetic analog of the end ...
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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 effects are mediated by slow genomic mechanisms through nuclear receptors as well as by fast nongenomic mechanisms through membrane-associated receptors and signaling cascades. The polypeptide hormones luteinizing hormone, follicle-stimulating hormone and gonadotropin-releasing hormone – each associated with the gonadotropin axis – are usually not regarded as sex hormones, although they play major sex-related roles. Production Natural sex hormones are made by the gonads (ovaries or testes), by adrenal glands, or by conversion from other sex steroids in other tissue such as liver or fat. Image:Steroidogenesis.svg Image:Biosinthesis of steroid hormones (simplified version).jpg Image:Biosinthesis of steroid hormones (extended version).jpg Im ...
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21-hydroxylase
Steroid 21-hydroxylase (also known as steroid 21-monooxygenase, cytochrome P450C21, 21α-hydroxylase and less commonly 21β-hydroxylase) is an enzyme that hydroxylates steroids at the C21 position and is involved in biosynthesis of aldosterone and cortisol. The enzyme converts progesterone and 17α-hydroxyprogesterone into 11-deoxycorticosterone and 11-deoxycortisol, respectively, within metabolic pathways that ultimately lead to aldosterone and cortisol. Deficiency in the enzyme may cause congenital adrenal hyperplasia. Steroid 21-hydroxylase is a member of the cytochrome P450 family of monooxygenase enzymes that uses an iron containing heme cofactor to oxidize substrates. The enzyme is localized in endoplasmic reticulum membranes of adrenal cortex, and is encoded by the gene in humans, which is located near the ''CYP21A1P'' pseudogene with high degree of sequence similarity. This similarity makes it difficult to analyze the gene at the molecular level, and sometimes leads to ...
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17α-hydroxylase
Cytochrome P450 17A1 (steroid 17α-monooxygenase, 17α-hydroxylase, 17-alpha-hydroxylase, 17,20-lyase, 17,20-desmolase) is an enzyme of the hydroxylase type that in humans is encoded by the ''CYP17A1'' gene on chromosome 10. It is ubiquitously expressed in many tissues and cell types, including the zona reticularis and zona fasciculata of the adrenal cortex as well as gonadal tissues. It has both 17α-hydroxylase and 17,20-lyase activities, and is a key enzyme in the steroidogenic pathway that produces progestins, mineralocorticoids, glucocorticoids, androgens, and estrogens. More specifically, the enzyme acts upon pregnenolone and progesterone to add a hydroxyl (-OH) group at carbon 17 position (C17) of the steroid D ring (the 17α-hydroxylase activity, ), or acts upon 17α-hydroxyprogesterone and 17α-hydroxypregnenolone to split the side-chain off the steroid nucleus (the 17,20-lyase activity, ). Structure Gene The ''CYP17A1'' gene resides on chromosome 10 at the band 10q24.3 a ...
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5α-reductase
5α-Reductases, also known as 3-oxo-5α-steroid 4-dehydrogenases, are enzymes involved in steroid metabolism. They participate in three metabolic pathways: bile acid biosynthesis, androgen and estrogen metabolism. There are three isozymes of 5α-reductase encoded by the genes SRD5A1, SRD5A2, and SRD5A3. 5α-Reductases catalyze the following generalized chemical reaction: :a 3-oxo-5α-steroid + acceptor a 3-oxo-Δ4-steroid + reduced acceptor Where a 3-oxo-5α-steroid and acceptor are substrates, and a corresponding 3-oxo-Δ4-steroid and the reduced acceptor are products. An instance of this generalized reaction that 5α-reductase type 2 catalyzes is: :dihydrotestosterone + NADP+ \rightleftharpoons testosterone + NADPH + H+ where dihydrotestosterone is the 3-oxo-5α-steroid, NADP+ is the acceptor and testosterone is the 3-oxo-Δ4-steroid and NADPH the reduced acceptor. Production and activity The enzyme is produced in many tissues in both males and females, in the r ...
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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 and the cyclic release of estrogen and progesterone. The uterine cycle governs the preparation and maintenance of the lining of the uterus (womb) to receive an embryo. These cycles are concurrent and coordinated, normally last between 21 and 35 days, with a median length of 28 days, and continue for about 30–45 years. Naturally occurring hormones drive the cycles; the cyclical rise and fall of the follicle stimulating hormone prompts the production and growth of oocytes (immature egg cells). The hormone estrogen stimulates the uterus lining ( endometrium) to thicken to accommodate an embryo should fertilization occur. The blood supply of the thickened lining provides nutrients to a successfully implanted embryo. If implantation does n ...
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Corticosteroid-binding Globulin
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 protein with corticosteroid-binding properties. This is the major transport protein for glucocorticoids and progestins in the blood of most vertebrates. The gene localizes to a chromosomal region containing several closely related serine protease inhibitors (serpins). Binding Transcortin binds several steroid hormones at high rates: * Cortisol - Approximately 90% of the cortisol in circulation is bound to transcortin. (The rest is bound to serum albumin.) Cortisol is thought to be biologically active only when it is not bound to transcortin. * Cortisone * Deoxycorticosterone (DOC) * Corticosterone - About 78% of serum corticosterone is bound to transcortin. * Aldosterone - Approximately 17% of serum aldosterone is bound to transcortin, while ...
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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 activity: estrone (E1), estradiol (E2), and estriol (E3). Estradiol, an estrane, is the most potent and prevalent. Another estrogen called estetrol (E4) is produced only during pregnancy. Estrogens are synthesized in all vertebrates and some insects. Their presence in both vertebrates and insects suggests that estrogenic sex hormones have an ancient evolutionary history. Quantitatively, estrogens circulate at lower levels than androgens in both men and women. While estrogen levels are significantly lower in males than in females, estrogens nevertheless have important physiological roles in males. Like all steroid hormones, estrogens readily diffuse across the cell membrane. Once inside the cell, they bind to and activate estrogen receptors (E ...
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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 can also occur through assisted reproductive technology procedures. A pregnancy may end in a live birth, a miscarriage, an induced abortion, or a stillbirth. Childbirth typically occurs around 40 weeks from the start of the last menstrual period (LMP), a span known as the gestational age. This is just over nine months. Counting by fertilization age, the length is about 38 weeks. Pregnancy is "the presence of an implanted human embryo or fetus in the uterus"; implantation occurs on average 8–9 days after fertilization. An '' embryo'' is the term for the developing offspring during the first seven weeks following implantation (i.e. ten weeks' gestational age), after which the term ''fetus'' is used until birth. Signs an ...
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