HOME

TheInfoList




Testosterone is the primary
sex hormone Sex hormones, also known as sex steroids, gonadocorticoids and gonadal steroids, are steroid hormone A steroid hormone is a steroid , hypothetical a steroid with 32 carbon atoms. Its core ring system (ABCD), composed of 17 carbon atoms, is ...
and
anabolic steroid Anabolic steroids, also known more properly as anabolic–androgenic steroids (AAS), are steroid A steroid is a biologically active organic compound In , organic compounds are generally any s that contain - . Due to carbon's ability t ...
in
males Male (symbol: ♂) is the sex of an organism that produces the gamete (sex cell) known as sperm, which fuses with the larger female gamete, or ovum, in the process of fertilization. A male organism cannot sexual reproduction, reproduce sexually ...
. In humans, testosterone plays a key role in the development of
male reproductive
male reproductive
tissues such as
testes Testicle or testis (plural testes) is the male Male (symbol: ♂) is the sex of an organism that produces the gamete (sex cell) known as sperm, which fuses with the larger female gamete, or ovum, in the process of fertilization. A male or ...

testes
and
prostate The prostate is both an accessory gland of the male reproductive system The male reproductive system consists of a number of sex organ A sex organ (or reproductive organ) is any part of an animal or plant that is involved in sexual repr ...

prostate
, as well as promoting
secondary sexual characteristic Secondary sex characteristics are features that appear during puberty Puberty is the process of physical changes through which a child Biologically, a child (plural children) is a human Humans (''Homo sapiens'') are the most ab ...
s such as increased
muscle Skeletal muscles (commonly referred to as muscles) are organs An organ is a group of tissues with similar functions. Plant life and animal life rely on many organs that co-exist in organ systems. A given organ's tissues can be broadly cat ...

muscle
and
bone A bone is a rigid tissue Tissue may refer to: Biology * Tissue (biology), an ensemble of similar cells that together carry out a specific function * ''Triphosa haesitata'', a species of geometer moth found in North America * ''Triphosa dubit ...

bone
mass, and the growth of
body hair Body hair, or androgenic hair, is the terminal hair that develops on the human body during and after puberty. It is differentiated from the head hair and less visible vellus hair, which is much finer and lighter in color. The growth of androgenic ...

body hair
. In addition, testosterone in both sexes is involved in health and well-being, including moods, behaviour, and in the prevention of
osteoporosis Osteoporosis is a systemic skeletal disorder characterized by low bone massImage:Bone density scanner.jpg, A scanner used to measure bone density using dual energy X-ray absorptiometry Bone density, or bone mineral density (BMD), is the amount ...
. Insufficient levels of testosterone in men may lead to abnormalities including frailty and bone loss. Testosterone is a
steroid A steroid is a biologically active organic compound In chemistry Chemistry is the study of the properties and behavior of . It is a that covers the that make up matter to the composed of s, s and s: their composition, structure, ...

steroid
from the
androstane Androstane is a C19 steroid with a gonane core. Androstane can exist as either of two isomers, known as 5α-androstane and 5β-androstane. File:androstane.png, 5α-Androstane File:androstane 5beta.png, 5β-Androstane Pharmacology 5α-Androstan ...

androstane
class containing a
ketone In chemistry Chemistry is the scientific Science () is a systematic enterprise that builds and organizes knowledge Knowledge is a familiarity or awareness, of someone or something, such as facts A fact is an occurrence i ...
and a
hydroxyl A hydroxy or hydroxyl group is a functional group with the chemical formula -OH and composed of one oxygen Oxygen is the chemical element Image:Simple Periodic Table Chart-blocks.svg, 400px, Periodic table, The periodic table of the ...

hydroxyl
group at positions three and seventeen respectively. It is
biosynthesized Biosynthesis is a multi-step, enzyme Enzymes () are proteins that act as biological catalysts (biocatalysts). Catalysts accelerate chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and ...

biosynthesized
in several steps from cholesterol and is converted in the liver to inactive metabolites. It exerts its action through binding to and activation of the
androgen receptor The androgen receptor (AR), also known as NR3C4 (nuclear receptor subfamily 3, group C, member 4), is a type of nuclear receptor In the field of molecular biology, nuclear receptors are a class of proteins found within cells that are responsi ...

androgen receptor
. In humans and most other
vertebrate Vertebrates () comprise all species of animal Animals (also called Metazoa) are multicellular A multicellular organism is an organism In biology, an organism () is any organic, life, living system that functions as an indiv ...
s, testosterone is secreted primarily by the
testicles Testicle or testis (plural testes) is the male Male (symbol: ♂) is the sex of an organism that produces the gamete (sex cell) known as sperm, which fuses with the larger female gamete, or ovum, in the process of fertilization. A male or ...

testicles
of males and, to a lesser extent, the
ovaries The ovary is an organ found in the female reproductive system 300px, 1. Labia_majora.html"_;"title="Vulva: 2. Labia_majora">Vulva: 2. Labia_majora; 3. Labia_minora; 4. Vulval_vestibule.html" "title="Labia_minora.html ...

ovaries
of
female Female (symbol: ♀) is the sex Sex is either of two divisions, typically male Male (♂) is the sex of an organism that produces the gamete known as sperm. A male gamete can fuse with a larger female gamete, or ovum, in the process of ...

female
s. On average, in adult males, levels of testosterone are about seven to eight times as great as in adult females. As the metabolism of testosterone in males is more pronounced, the daily production is about 20 times greater in men. Females are also more sensitive to the hormone. In addition to its role as a natural hormone, testosterone is used as a
medication A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to medical diagnosis, diagnose, cure, therapy, treat, or preventive medicine, prevent disease. Drug therapy (pharmacotherapy) ...

medication
in the treatment of
hypogonadism Hypogonadism means diminished functional activity of the gonad A gonad, sex gland, or reproductive gland is a mixed gland that produces the gametes (sex cells) and sex hormones of an organism. In the female of the species the reproductive cell ...
in men and
breast cancer Breast cancer is cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumor A benign tumor is a mass of cells Cell most o ...

breast cancer
in women. Since testosterone levels decrease as men age, testosterone is sometimes used in older men to counteract this deficiency. It is also used illicitly to enhance physique and performance, for instance in
athlete An athlete (also sportsman or sportswoman) is a person who competes in one or more sports that involve physical strength, speed or endurance. The use of the term in several sports, such as golf or auto racing, becomes a controversial issue. A ...

athlete
s. The
World Anti-Doping Agency The World Anti-Doping Agency (WADA; french: Agence mondiale antidopage, link=no, AMA) is a foundation initiated by the International Olympic Committee based in Canada to promote, coordinate, and monitor the fight against drugs in sports. The age ...
is listing it as S1 Anabolic agent substance "prohibited at all times".


Biological effects

In general,
androgens An androgen (from Greek ''andr-'', the stem of the word meaning "man") is any natural or synthetic steroid hormone A steroid hormone is a steroid A steroid is a biologically active organic compound In , organic compounds are genera ...
such as testosterone promote
protein synthesis Protein biosynthesis (or protein synthesis) is a core biological process, occurring inside Cell (biology), cells, homeostasis, balancing the loss of cellular proteins (via Proteolysis, degradation or Protein targeting, export) through the product ...

protein synthesis
and thus growth of tissues with
androgen receptors The androgen receptor (AR), also known as NR3C4 (nuclear receptor subfamily 3, group C, member 4), is a type of nuclear receptor In the field of molecular biology, nuclear receptors are a class of proteins found within cells that are responsi ...
. Testosterone can be described as having virilising and
anabolic Anabolism () is the set of metabolic pathway In biochemistry, a metabolic pathway is a linked series of chemical reaction A chemical reaction is a process that leads to the IUPAC nomenclature for organic transformations, chemical transformation ...
effects (though these categorical descriptions are somewhat arbitrary, as there is a great deal of mutual overlap between them). * ''Anabolic effects'' include growth of
muscle mass Skeletal muscles (commonly referred to as muscles) are organs An organ is a group of tissues with similar functions. Plant life and animal life rely on many organs that co-exist in organ systems. A given organ's tissues can be broadly cate ...
and strength, increased
bone density Bone density, or bone mineral density (BMD), is the amount of bone mineral Bone mineral (also called inorganic bone phase, bone salt, or bone apatite) is the inorganic In chemistry Chemistry is the scientific discipline involved with Chemic ...

bone density
and strength, and stimulation of linear growth and
bone maturation Bone age is the degree of maturation of a child's bones. As a person grows from Fetus, fetal life through childhood, puberty, and finishes growth as a young adult, the bones of the skeleton change in size and shape. These changes can be seen by x-ra ...
. * ''Androgenic effects'' include maturation of the
sex organs A sex organ (or reproductive organ) is any part of an animal or plant that is involved in sexual reproduction Sexual reproduction is a type of reproduction Reproduction (or procreation or breeding) is the biological process Biological ...
, particularly the
penis A penis (plural ''penises'' or ''penes'' () is the primary sexual organ that male animals use to inseminate females (or hermaphrodites) during Copulation (zoology), copulation. Such organs occur in many animals, both #Vertebrates, vertebrate ...

penis
and the formation of the
scrotum The scrotum or scrotal sac is an Anatomy, anatomical male reproductive structure located at the base of the penis that consists of a suspended dual-chambered sac of skin and smooth muscle. It is present in most terrestrial male mammals. The scr ...

scrotum
in the fetus, and after birth (usually at
puberty Puberty is the process of physical changes through which a child Biologically, a child (plural children) is a human Humans (''Homo sapiens'') are the most abundant and widespread species In biology Biology is the natur ...

puberty
) a deepening of the
voice The human voice consists of sound In physics Physics is the that studies , its , its and behavior through , and the related entities of and . "Physical science is that department of knowledge which relates to the order of natu ...
, growth of
facial hair Facial hair is hair Hair is a protein filament In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecular biology, molec ...
(such as the
beard A beard is the hair that grows on the jaw, chin, upper lip, lower lip, cheeks, and neck of humans and some non-human animals. In humans, usually only pubescent or adult males are able to grow beards. Some women with hirsutism Hirsutism is e ...

beard
) and axillary (underarm) hair. Many of these fall into the category of male
secondary sex characteristics Secondary sex characteristics are features that appear during puberty in humans, and at sexual maturity in other animals. These characteristics are particularly evident in the sexual dimorphism, sexually dimorphic phenotypic traits that distinguis ...
. Testosterone effects can also be classified by the age of usual occurrence. For
postnatal The postpartum (or postnatal) period begins immediately after childbirth Childbirth, also known as labour or delivery, is the ending of pregnancy Pregnancy, also known as gestation, is the time during which one or more offspring In ...
effects in both males and females, these are mostly dependent on the levels and duration of circulating free testosterone.


Before birth

Effects before birth are divided into two categories, classified in relation to the stages of development. The first period occurs between 4 and 6 weeks of the gestation. Examples include genital virilisation such as midline fusion,
phallic A phallus is a penis (especially when Erection, erect), an object that resembles a penis, or a mimesis, mimetic image of an erect penis. In art history a figure with an erect penis is described as ithyphallic. Any object that symbolically— ...

phallic
urethra The urethra (from Greek#REDIRECT Greek Greek may refer to: Greece Anything of, from, or related to Greece Greece ( el, Ελλάδα, , ), officially the Hellenic Republic, is a country located in Southeast Europe. Its population is appro ...

urethra
,
scrotal The scrotum or scrotal sac is an Anatomy, anatomical male reproductive structure located at the base of the penis that consists of a suspended dual-chambered sac of skin and smooth muscle. It is present in most terrestrial male mammals. The scr ...

scrotal
thinning and rugation, and
phallic A phallus is a penis (especially when Erection, erect), an object that resembles a penis, or a mimesis, mimetic image of an erect penis. In art history a figure with an erect penis is described as ithyphallic. Any object that symbolically— ...
enlargement; although the role of testosterone is far smaller than that of
dihydrotestosterone Dihydrotestosterone (DHT, 5α-dihydrotestosterone, 5α-DHT, androstanolone or stanolone) is an endogenous Endogenous substances and processes are those that originate from within a system such as an organism, Tissue (biology), tissue, or Cell ...
. There is also development of the
prostate The prostate is both an accessory gland of the male reproductive system The male reproductive system consists of a number of sex organ A sex organ (or reproductive organ) is any part of an animal or plant that is involved in sexual repr ...

prostate
gland and
seminal vesicle The seminal vesicles (also called vesicular glands, or seminal glands) are a pair of two convoluted tubular glands that lie behind the urinary bladder The urinary bladder, or simply bladder, is a hollow muscular MUSCULAR (DS-200B), located i ...
s. During the second trimester, androgen level is associated with
sex Sex is either of two divisions, typically male Male (♂) is the sex of an organism that produces the gamete known as sperm. A male gamete can fuse with a larger female gamete, or ovum, in the process of fertilization. A male cannot sexual r ...
formation. Specifically, testosterone, along with anti-Müllerian hormone (AMH) promote growth of the Wolffian duct and degeneration of the Müllerian duct respectively. This period affects the femininization or masculinization of the fetus and can be a better predictor of feminine or masculine behaviours such as sex typed behaviour than an adult's own levels. Prenatal androgens apparently influence interests and engagement in gendered activities and have moderate effects on spatial abilities. Among women with , a male-typical play in childhood correlated with reduced satisfaction with the female gender and reduced heterosexual interest in adulthood.


Early infancy

Early infancy androgen effects are the least understood. In the first weeks of life for male infants, testosterone levels rise. The levels remain in a pubertal range for a few months, but usually reach the barely detectable levels of childhood by 4–7 months of age. The function of this rise in humans is unknown. It has been theorized that brain
masculinization Virilization or masculinization is the biological development of adult male characteristics in young males or females. Most of the changes of virilization are produced by androgens. Virilization is most commonly used in three medical and Sex diff ...
is occurring since no significant changes have been identified in other parts of the body. The male brain is masculinized by the aromatization of testosterone into
estrogen Estrogens or oestrogens, are a class of natural or synthetic sex hormone Sex hormones, also known as sex steroids, gonadocorticoids and gonadal steroids, are steroid hormone A steroid hormone is a steroid that acts as a hormone. Steroid ho ...

estrogen
, which crosses the
blood–brain barrier The blood–brain barrier (BBB) is a highly selective semipermeable border of endothelial cells Endothelium is a single layer of squamous Epithelium () is one of the four basic types of animal Animals (also called Metazoa) are mu ...
and enters the male brain, whereas female fetuses have α-fetoprotein, which binds the estrogen so that female brains are not affected.


Before puberty

Before puberty, effects of rising androgen levels occur in both boys and girls. These include adult-type
body odor Body odor is present in all animals, including humans Humans (''Homo sapiens'') are the most populous and widespread species In biology, a species is the basic unit of biological classification, classification and a taxonomic rank of ...
, increased oiliness of skin and hair,
acne Acne, also known as acne vulgaris, is a long-term skin condition A skin condition, also known as cutaneous condition, is any medical condition A disease is a particular abnormal condition that negatively affects the structure or ...

acne
,
pubarche Pubarche refers to the first appearance of pubic hair Pubic hair is terminal body hair that is found in the genital area of adolescent and adult humans. The hair is located on and around the sex organs and sometimes at the top of the inside ...
(appearance of
pubic hair Pubic hair is terminal body hair that is found in the genital area of adolescent and adult humans. The hair is located on and around the sex organs and sometimes at the top of the inside of the thighs. In the pubic region around the pubis ...

pubic hair
), axillary hair (armpit hair),
growth spurt Human height or stature is the distance from the bottom of the feet to the top of the head in a human body The human body is the structure of a human being Humans (''Homo sapiens'') are the most abundant and widespread species ...
, accelerated
bone maturation Bone age is the degree of maturation of a child's bones. As a person grows from Fetus, fetal life through childhood, puberty, and finishes growth as a young adult, the bones of the skeleton change in size and shape. These changes can be seen by x-ra ...
, and
facial hair Facial hair is hair Hair is a protein filament In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecular biology, molec ...
.


Pubertal

effects begin to occur when androgen has been higher than normal adult female levels for months or years. In males, these are usual late pubertal effects, and occur in women after prolonged periods of heightened levels of free testosterone in the
blood Blood is a body fluid Body fluids, bodily fluids, or biofluids are liquid A liquid is a nearly incompressible In fluid mechanics or more generally continuum mechanics, incompressible flow (isochoric process, isochoric flow) refers t ...

blood
. The effects include: * Growth of
spermatogenic Spermatogenesis is the process by which haploid Ploidy () is the number of complete sets of chromosome A chromosome is a long DNA molecule with part or all of the genetic material of an organism. Most eukaryotic chromosomes include p ...
tissue in testicles, male
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 Demography, demographicall ...
,
penis A penis (plural ''penises'' or ''penes'' () is the primary sexual organ that male animals use to inseminate females (or hermaphrodites) during Copulation (zoology), copulation. Such organs occur in many animals, both #Vertebrates, vertebrate ...

penis
or
clitoris The clitoris ( or ) is a female sex organ present in mammals, ostriches and a limited number of #Other animals, other animals. In humans, the visible portion – the glans – is at the front junction of the labia minora (inner lips), ...

clitoris
enlargement, increased
libido Libido (; colloquial Colloquialism or colloquial language is the style (sociolinguistics), linguistic style used for casual (informal) communication. It is the most common functional style of speech, the idiom normally employed in conversation ...
and frequency of
erection An erection (clinically: penile erection or penile tumescence) is a physiological phenomenon in which the penis A penis (plural ''penises'' or ''penes'' () is the primary sexual organ that male animals use to inseminate females (or h ...

erection
or clitoral engorgement occurs. * Growth of
jaw The jaw is any opposable articulated structure at the entrance of the mouth In animal anatomy Anatomy (Greek ''anatomē'', 'dissection') is the branch of biology concerned with the study of the structure of organisms and their parts. Ana ...

jaw
, brow, chin, and nose and remodeling of facial bone contours, in conjunction with
human growth hormone Growth hormone (GH) or somatotropin, also known as human growth hormone (hGH or HGH) in its human form, is a peptide hormonePeptide hormones or protein hormones are hormones whose molecules are peptides or proteins, respectively. The latter ha ...
occurs. * Completion of bone maturation and termination of growth. This occurs indirectly via
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 cycle, estrous and menstrual cycle, menstrual female reproductive cycles. Estradiol is resp ...

estradiol
metabolites In biochemistry Biochemistry or biological chemistry, is the study of es within and relating to living s. A sub-discipline of both and , biochemistry may be divided into three fields: , and . Over the last decades of the 20th century, bio ...

metabolites
and hence more gradually in men than women. * Increased muscle strength and mass, shoulders become broader and rib cage expands, deepening of voice, growth of the
Adam's apple The Adam's apple or laryngeal prominence, is the lump or protrusion in the human neck The neck is the part of the body on many vertebrate Vertebrates () comprise all species of animal Animals (also called Metazoa) are multicellular ...
. * Enlargement of
sebaceous glands A sebaceous gland is a microscopic exocrine Exocrine glands are gland In animals, a gland is a group of cells in an animal's body that synthesizes substances (such as hormone A hormone (from the Greek participle , "setting in motion") is a ...
. This might cause acne, subcutaneous
fat In nutrition Nutrition is the biochemical Biochemistry or biological chemistry, is the study of chemical processes within and relating to living organisms. A sub-discipline of both chemistry and biology, biochemistry may be divided ...
in face decreases. * Pubic hair extends to thighs and up toward , development of
facial hair Facial hair is hair Hair is a protein filament In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecular biology, molec ...
(
sideburns Sideburns, sideboards, or side whiskers are facial hair Facial hair is hair Hair is a protein filament In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structur ...

sideburns
,
beard A beard is the hair that grows on the jaw, chin, upper lip, lower lip, cheeks, and neck of humans and some non-human animals. In humans, usually only pubescent or adult males are able to grow beards. Some women with hirsutism Hirsutism is e ...

beard
,
moustache A moustache (; en-US, mustache, ) is a strip of facial hair grown above the upper lip. Moustaches have been worn in various styles throughout history. Etymology The word "moustache" is French language, French, and is derived from the Itali ...

moustache
), loss of scalp hair (androgenetic alopecia), increase in
chest hair Chest hair is hair that grows on the chest of a male in the region between the neck and the Human abdomen, abdomen. Chest hair develops during and after puberty along with other types of androgenic hair. Development and growth Although vellus ...
, periareolar hair,
perianal The anus (from Latin Latin (, or , ) is a classical language belonging to the Italic languages, Italic branch of the Indo-European languages. Latin was originally spoken in the area around Rome, known as Latium. Through the power of the Rom ...
hair,
leg hair Leg hair is hair that grows on the legs of humans, generally appearing after 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 initia ...

leg hair
,
armpit hair Underarm hair, also known as axillary hair, is the hair Hair is a protein filament In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemi ...
.


Adult

Testosterone is necessary for normal
sperm Sperm is the male reproductive Cell (biology), 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 ...

sperm
development. It activates genes in
Sertoli cell A Sertoli cell (a kind of sustentacular cell A sustentacular cell is a type of cell primarily associated with structural support, they can be found in various tissues. * Sustentacular cells of the olfactory epithelium The olfactory epithelium ...
s, which promote differentiation of
spermatogonia A spermatogonium (plural: ''spermatogonia'') is an undifferentiated male germ cell A germ cell is any biological cell The cell (from Latin ''cella'', meaning "small room") is the basic structural, functional, and biological unit of all kno ...
. It regulates acute HPA (
hypothalamic–pituitary–adrenal axis The hypothalamic–pituitary–adrenal axis (HPA axis or HTPA axis) is a complex set of direct influences and feedback Feedback occurs when outputs of a system are routed back as inputs as part of a Signal chain (signal processing chain), chai ...
) response under dominance challenge. Androgens including testosterone enhance muscle growth. Testosterone also regulates the population of receptors on
megakaryocytes A megakaryocyte (''mega- Mega is a unit prefixA unit prefix is a specifier or mnemonic that is prepended to units of measurement to indicate multiples or fractions of the units. Units of various order of magnitude, sizes are commonly formed by th ...
and
platelets Platelets, also called thrombocytes (from Greek#REDIRECT Greek Greek may refer to: Greece Anything of, from, or related to Greece Greece ( el, Ελλάδα, , ), officially the Hellenic Republic, is a country located in Southeast Europe. ...

platelets
and hence platelet aggregation in humans. Adult testosterone effects are more clearly demonstrable in males than in females, but are likely important to both sexes. Some of these effects may decline as testosterone levels might decrease in the later decades of adult life.


Health risks

Testosterone does not appear to increase the risk of developing
prostate cancer Prostate cancer is cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumor A benign tumor is a mass of cells Cell most o ...

prostate cancer
. In people who have undergone testosterone deprivation therapy, testosterone increases beyond the castrate level have been shown to increase the rate of spread of an existing prostate cancer. Conflicting results have been obtained concerning the importance of testosterone in maintaining cardiovascular health. Nevertheless, maintaining normal testosterone levels in elderly men has been shown to improve many parameters that are thought to reduce cardiovascular disease risk, such as increased lean body mass, decreased visceral fat mass, decreased total cholesterol, and glycemic control. High androgen levels are associated with
menstrual cycle The menstrual cycle is a series of natural changes in hormone A hormone (from the Greek Greek may refer to: Greece Anything of, from, or related to Greece Greece ( el, Ελλάδα, , ), officially the Hellenic Republic, is a country l ...

menstrual cycle
irregularities in both clinical populations and healthy women.


Sexual arousal

Testosterone levels follow a nycthemeral rhythm that peaks early each day, regardless of sexual activity. There are positive correlations between positive orgasm experience in women and testosterone levels where relaxation was a key perception of the experience. There is no correlation between testosterone and men's perceptions of their orgasm experience, and also no correlation between higher testosterone levels and greater sexual assertiveness in either sex. Sexual arousal and
masturbation Masturbation ( ) is the sexual stimulation Sexual stimulation is any stimulus (including bodily contact) that leads to, enhances and maintains sexual arousal, and may lead to orgasm Orgasm (from Ancient Greek, Greek ὀργασμός ' ...

masturbation
in women produce small increases in testosterone concentrations. The
plasma Plasma or plasm may refer to: Science * Plasma (physics), one of the four fundamental states of matter * Plasma (mineral) or heliotrope, a mineral aggregate * Quark–gluon plasma, a state of matter in quantum chromodynamics Biology * Blood plasma ...
levels of various
steroids 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 which alter membrane fluidity; and ...
significantly increase after masturbation in men and the testosterone levels correlate to those levels.


Mammalian studies

Studies conducted in rats have indicated that their degree of sexual arousal is sensitive to reductions in testosterone. When testosterone-deprived rats were given medium levels of testosterone, their sexual behaviours (copulation, partner preference, etc.) resumed, but not when given low amounts of the same hormone. Therefore, these mammals may provide a model for studying clinical populations among humans suffering from sexual arousal deficits such as
hypoactive sexual desire disorder #REDIRECT Hypoactive sexual desire disorder Hypoactive sexual desire disorder (HSDD), hyposexuality or inhibited sexual desire (ISD) is considered a sexual dysfunction and is characterized as a lack or absence of sexual fantasies and desire for s ...
. Every mammalian species examined demonstrated a marked increase in a male's testosterone level upon encountering a ''novel'' female. The reflexive testosterone increases in male mice is related to the male's initial level of sexual arousal. In non-human primates, it may be that testosterone in puberty stimulates sexual arousal, which allows the primate to increasingly seek out sexual experiences with females and thus creates a sexual preference for females. Some research has also indicated that if testosterone is eliminated in an adult male human or other adult male primate's system, its sexual motivation decreases, but there is no corresponding decrease in ability to engage in sexual activity (mounting, ejaculating, etc.). In accordance with
sperm competition Sperm competition is the competitive process between spermatozoa A spermatozoon (pronounced , alternate spelling spermatozoön; plural spermatozoa; from grc, σπέρμα ("seed") and grc, ζῷον ("living being")) is a motile Motilit ...
theory, testosterone levels are shown to increase as a response to previously neutral stimuli when conditioned to become sexual in male rats. This reaction engages penile reflexes (such as erection and ejaculation) that aid in sperm competition when more than one male is present in mating encounters, allowing for more production of successful sperm and a higher chance of reproduction.


Males

In men, higher levels of testosterone are associated with periods of sexual activity. Men who watch a sexually explicit movie have an average increase of 35% in testosterone, peaking at 60–90 minutes after the end of the film, but no increase is seen in men who watch sexually neutral films. Men who watch sexually explicit films also report increased motivation, competitiveness, and decreased exhaustion. A link has also been found between relaxation following sexual arousal and testosterone levels. Men's levels of testosterone, a hormone known to affect men's mating behaviour, changes depending on whether they are exposed to an or nonovulating woman's body odour. Men who are exposed to scents of ovulating women maintained a stable testosterone level that was higher than the testosterone level of men exposed to nonovulation cues. Men are heavily aware of hormone cycles in females. This may be linked to the ''ovulatory shift hypothesis'', where males are adapted to respond to the ovulation cycles of females by sensing when they are most fertile and whereby females look for preferred male mates when they are the most fertile; both actions may be driven by hormones.


Females

Androgens may modulate the physiology of vaginal tissue and contribute to female genital sexual arousal. Women's level of testosterone is higher when measured pre-intercourse vs pre-cuddling, as well as post-intercourse vs post-cuddling. There is a time lag effect when testosterone is administered, on genital arousal in women. In addition, a continuous increase in vaginal sexual arousal may result in higher genital sensations and sexual appetitive behaviors. When females have a higher baseline level of testosterone, they have higher increases in sexual arousal levels but smaller increases in testosterone, indicating a ceiling effect on testosterone levels in females. Sexual thoughts also change the level of testosterone but not the level of cortisol in the female body, and hormonal contraceptives may affect the variation in testosterone response to sexual thoughts. Testosterone may prove to be an effective treatment in
female sexual arousal disorder Female sexual arousal disorder (FSAD) is a disorder characterized by a persistent or recurrent inability to attain sexual arousal Sexual arousal (also sexual excitement) describes the physiological Physiology (; ) is the scientific ...
s, and is available as a
dermal patch A dermal patch or skin patch is a medicated A medication (also referred to as medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug File:Aspirine macro shot.jpg, Uncoated aspirin Tablet (pharmacy), tablets, consistin ...
. There is no FDA approved androgen preparation for the treatment of androgen insufficiency; however, it has been used as an
off-label use Off-label use is the use of pharmaceutical drug A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug Uncoated tablets, consisting of about 90% acetylsalicylic acid, along wit ...
to treat low
libido Libido (; colloquial Colloquialism or colloquial language is the style (sociolinguistics), linguistic style used for casual (informal) communication. It is the most common functional style of speech, the idiom normally employed in conversation ...
and
sexual dysfunction Sexual dysfunction is difficulty experienced by an individual or partners during any stage of normal sexual activity Human sexual activity, human sexual practice or human sexual behaviour is the manner in which humans experience and expres ...
in older women. Testosterone may be a treatment for postmenopausal women as long as they are effectively estrogenized.


Romantic relationships

Falling in love Falling in love is the development of strong feelings of attachment and love, usually towards another person. The term is metaphorical, emphasizing that the process, like the physical act of falling, is sudden, uncontrollable and leaves the l ...

Falling in love
decreases men's testosterone levels while increasing women's testosterone levels. There has been speculation that these changes in testosterone result in the temporary reduction of differences in behavior between the sexes. However, it is suggested that after the "honeymoon phase" ends—about four years into a relationship—this change in testosterone levels is no longer apparent. Men who produce less testosterone are more likely to be in a relationship or married, and men who produce more testosterone are more likely to divorce. Marriage or commitment could cause a decrease in testosterone levels. Single men who have not had relationship experience have lower testosterone levels than single men with experience. It is suggested that these single men with prior experience are in a more competitive state than their non-experienced counterparts. Married men who engage in bond-maintenance activities such as spending the day with their spouse and/or child have no different testosterone levels compared to times when they do not engage in such activities. Collectively, these results suggest that the presence of competitive activities rather than bond-maintenance activities are more relevant to changes in testosterone levels. Men who produce more testosterone are more likely to engage in extramarital sex. Testosterone levels do not rely on physical presence of a partner; testosterone levels of men engaging in same-city and long-distance relationships are similar. Physical presence may be required for women who are in relationships for the testosterone–partner interaction, where same-city partnered women have lower testosterone levels than long-distance partnered women.


Fatherhood

Fatherhood decreases testosterone levels in men, suggesting that the emotions and behaviour tied to decreased testosterone promote paternal care. In humans and other species that utilize allomaternal care, paternal investment in offspring is beneficial to said offspring's survival because it allows the parental
dyad Dyad or dyade may refer to: * Dyad (biology), a pair of sister chromatids * Dyad (music), a set of two notes or pitches * Dyad (Greek philosophy), Greek philosophers' principle of "twoness" or "otherness" * Dyad (sociology), a group of two people ...
to raise multiple children simultaneously. This increases the reproductive fitness of the parents because their offspring are more likely to survive and reproduce. Paternal care increases offspring survival due to increased access to higher quality food and reduced physical and immunological threats. This is particularly beneficial for humans since offspring are dependent on parents for extended periods of time and mothers have relatively short inter-birth intervals. While the extent of paternal care varies between cultures, higher investment in direct child care has been seen to be correlated with lower average testosterone levels as well as temporary fluctuations. For instance, fluctuation in testosterone levels when a child is in distress has been found to be indicative of fathering styles. If a father's testosterone levels decrease in response to hearing their baby cry, it is an indication of empathizing with the baby. This is associated with increased nurturing behavior and better outcomes for the infant.


Motivation

Testosterone levels play a major role in risk-taking during financial decisions.


Aggression and criminality

Most studies support a link between adult criminality and testosterone. Nearly all studies of juvenile delinquency and testosterone are not significant. Most studies have also found testosterone to be associated with behaviors or personality traits linked with criminality such as
antisocial behavior Antisocial may refer to: Sociology, psychiatry and psychology *Anti-social behaviour Anti-social behaviours are actions that harm or lack consideration for the well-being of others. It has also been defined as any type of conduct that violate ...
and
alcoholism Alcoholism is, broadly, any drinking of alcohol In , alcohol is an that carries at least one (−OH) bound to a atom. The term alcohol originally referred to the primary alcohol (ethyl alcohol), which is and is the main alcoho ...
. Many studies have also been done on the relationship between more general aggressive behavior and feelings and testosterone. About half the studies have found a relationship and about half no relationship. Studies have also found that testosterone facilitates aggression by modulating
vasopressin Vasopressin, also called antidiuretic hormone (ADH), arginine vasopressin (AVP) or argipressin, is a hormone A hormone (from the Greek Greek may refer to: Greece Anything of, from, or related to Greece Greece ( el, Ελλάδα, , ...

vasopressin
receptors in the
hypothalamus The hypothalamus (from Ancient Greek wikt:ὑπό, ὑπό, "under", and wikt:θάλαμος, θάλαμος, "chamber") is a portion of the brain that contains a number of small Nucleus (neuroanatomy), nuclei with a variety of functions. One of ...

hypothalamus
. Testosterone is significantly discussed in relation to aggression and competitive behavior. There are two theories on the role of testosterone in aggression and competition. The first one is the challenge hypothesis which states that testosterone would increase during puberty, thus facilitating reproductive and competitive behavior which would include aggression. It is therefore the challenge of competition among males of the species that facilitates aggression and violence. Studies conducted have found direct correlation between testosterone and dominance, especially among the most violent criminals in prison who had the highest testosterone levels. The same research also found fathers (those outside competitive environments) had the lowest testosterone levels compared to other males. The second theory is similar and is known as " evolutionary neuroandrogenic (ENA) theory of male aggression". Testosterone and other androgens have evolved to masculinize a brain in order to be competitive even to the point of risking harm to the person and others. By doing so, individuals with masculinized brains as a result of pre-natal and adult life testosterone and androgens enhance their resource acquiring abilities in order to survive, attract and copulate with mates as much as possible. The masculinization of the brain is not just mediated by testosterone levels at the adult stage, but also testosterone exposure in the womb as a fetus. Higher pre-natal testosterone indicated by a low
digit ratio The digit ratio is the ratio of the lengths of different digits or fingers. The 2D:4D ratio is the most studied digit ratio and is calculated by dividing the length of the index finger of a given hand by the length of the ring finger of the sam ...
as well as adult testosterone levels increased risk of fouls or aggression among male players in a soccer game. Studies have also found higher pre-natal testosterone or lower digit ratio to be correlated with higher aggression in males. The rise in testosterone levels during competition predicted aggression in males but not in females. Subjects who interacted with hand guns and an experimental game showed rise in testosterone and aggression. Natural selection might have evolved males to be more sensitive to competitive and status challenge situations and that the interacting roles of testosterone are the essential ingredient for aggressive behaviour in these situations. Testosterone mediates attraction to cruel and violent cues in men by promoting extended viewing of violent stimuli. Testosterone specific structural brain characteristic can predict aggressive behaviour in individuals. Testosterone might encourage fair behavior. For one study, subjects took part in a behavioral experiment where the distribution of a real amount of money was decided. The rules allowed both fair and unfair offers. The negotiating partner could subsequently accept or decline the offer. The fairer the offer, the less probable a refusal by the negotiating partner. If no agreement was reached, neither party earned anything. Test subjects with an artificially enhanced testosterone level generally made better, fairer offers than those who received placebos, thus reducing the risk of a rejection of their offer to a minimum. Two later studies have empirically confirmed these results. However men with high testosterone were significantly 27% less generous in an ultimatum game. The Annual NY Academy of Sciences has also found anabolic steroid use (which increases testosterone) to be higher in teenagers, and this was associated with increased violence. Studies have also found administered testosterone to increase verbal aggression and anger in some participants. A few studies indicate that the testosterone derivative
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 cycle, estrous and menstrual cycle, menstrual female reproductive cycles. Estradiol is resp ...

estradiol
(one form of
estrogen Estrogens or oestrogens, are a class of natural or synthetic sex hormone Sex hormones, also known as sex steroids, gonadocorticoids and gonadal steroids, are steroid hormone A steroid hormone is a steroid that acts as a hormone. Steroid ho ...

estrogen
) might play an important role in male aggression. Estradiol is known to correlate with aggression in male mice. Moreover, the conversion of testosterone to estradiol regulates male aggression in sparrows during breeding season. Rats who were given anabolic steroids that increase testosterone were also more physically aggressive to provocation as a result of "threat sensitivity". The relationship between testosterone and aggression may also function indirectly, as it has been proposed that testosterone does not amplify tendencies towards aggression but rather amplifies whatever tendencies will allow an individual to maintain social status when challenged. In most animals, aggression is the means of maintaining social status. However, humans have multiple ways of obtaining social status. This could explain why some studies find a link between testosterone and pro-social behaviour if pro-social behaviour is rewarded with social status. Thus the link between testosterone and aggression and violence is due to these being rewarded with social status. The relationship may also be one of a "permissive effect" whereby testosterone does elevate aggression levels but only in the sense of allowing average aggression levels to be maintained; chemically or physically castrating the individual will reduce aggression levels (though it will not eliminate them) but the individual only needs a small-level of pre-castration testosterone to have aggression levels to return to normal, which they will remain at even if additional testosterone is added. Testosterone may also simply exaggerate or amplify existing aggression; for example, chimpanzees who receive testosterone increases become more aggressive to chimps lower than them in the social hierarchy but will still be submissive to chimps higher than them. Testosterone thus does not make the chimpanzee indiscriminately aggressive but instead amplifies his pre-existing aggression towards lower-ranked chimps. In humans, testosterone appears more to promote status-seeking and social dominance than simply increasing physical aggression. When controlling for the effects of belief in having received testosterone, women who have received testosterone make fairer offers than women who have not received testosterone.


Brain

The brain is also affected by this sexual differentiation; the
enzyme Enzymes () are proteins that act as biological catalysts (biocatalysts). Catalysts accelerate chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates in ...

enzyme
aromatase Aromatase, also called estrogen synthetase or estrogen synthase, is an enzyme Enzymes () are proteins that act as biological catalysts (biocatalysts). Catalysts accelerate chemical reactions. The molecules upon which enzymes may act are cal ...
converts testosterone into
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 cycle, estrous and menstrual cycle, menstrual female reproductive cycles. Estradiol is resp ...

estradiol
that is responsible for
masculinization Virilization or masculinization is the biological development of adult male characteristics in young males or females. Most of the changes of virilization are produced by androgens. Virilization is most commonly used in three medical and Sex diff ...
of the brain in male mice. In humans, masculinization of the fetal brain appears, by observation of gender preference in patients with
congenital disease A birth defect, also known as a congenital disorder, is a condition present at birth 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 initiat ...
s of androgen formation or androgen receptor function, to be associated with functional androgen receptors. There are some differences between a male and female brain (possibly the result of different testosterone levels), one of them being size: the male human brain is, on average, larger. Men were found to have a total myelinated fiber length of 176 000 km at the age of 20, whereas in women the total length was 149 000 km (approx. 15% less). No immediate short term effects on mood or behavior were found from the administration of supraphysiologic doses of testosterone for 10 weeks on 43 healthy men. A correlation between testosterone and risk tolerance in career choice exists among women. Attention, memory, and spatial ability are key cognitive functions affected by testosterone in humans. Preliminary evidence suggests that low testosterone levels may be a risk factor for cognitive decline and possibly for dementia of the Alzheimer's type, a key argument in life extension medicine for the use of testosterone in anti-aging therapies. Much of the literature, however, suggests a curvilinear or even quadratic relationship between spatial performance and circulating testosterone, where both hypo- and hypersecretion (deficient- and excessive-secretion) of circulating androgens have negative effects on cognition.


Immune system and inflammation

Testosterone deficiency is associated with an increased risk of metabolic syndrome, cardiovascular disease and Mortality rate, mortality, which are also sequelae of chronic inflammation. Testosterone plasma concentration inversely correlates to multiple biomarkers of inflammation including C-reactive protein, CRP, interleukin 1 beta, interleukin 6, TNF alpha and endotoxin concentration, as well as leukocyte count. As demonstrated by a meta-analysis, substitution therapy with testosterone results in a significant reduction of inflammatory markers. These effects are mediated by different mechanisms with synergistic action. In androgen-deficient men with concomitant autoimmune thyroiditis, substitution therapy with testosterone leads to a decrease in thyroid autoantibody titres and an increase in thyroid's secretory capacity (SPINA-GT).


Medical use

Testosterone is used as a medication for the treatment of male hypogonadism, gender dysphoria, and certain types of
breast cancer Breast cancer is cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumor A benign tumor is a mass of cells Cell most o ...

breast cancer
. This is known as hormone replacement therapy (HRT) or testosterone replacement therapy (TRT), which maintains serum testosterone levels in the normal range. andropause, Decline of testosterone production with age has led to interest in androgen replacement therapy. It is unclear if the use of testosterone for low levels due to aging is beneficial or harmful. Testosterone is included in the WHO Model List of Essential Medicines, World Health Organization's list of essential medicines, which are the most important medications needed in a basic health system. It is available as a generic medication. It can be administered as a cream or transdermal patch that is applied to the skin, by intramuscular injection, injection into a muscle, as a tablet that is Buccal administration, placed in the cheek, or by ingestion. Common side effects from testosterone medication include acne, swelling (medical), swelling, and gynecomastia, breast enlargement in males. Serious side effects may include liver toxicity, heart disease, and behavioral changes. Women and children who are exposed may develop virilization. It is recommended that individuals with
prostate cancer Prostate cancer is cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumor A benign tumor is a mass of cells Cell most o ...

prostate cancer
not use the medication. It can cause harm if used during pregnancy or breastfeeding. 2020 guidelines from the American College of Physicians support the discussion of testosterone (medication), testosterone treatment in adult men with age-related Low T, low levels of testosterone who have sexual dysfunction. They recommend yearly evaluation regarding possible improvement and, if none, to discontinue testosterone; physicians should consider intramuscular treatments, rather than transdermal treatments, due to costs and since the effectiveness and harm of either method is similar. Testosterone treatment for reasons other than possible improvement of sexual dysfunction may not be recommended.


Biological activity


Free testosterone

Lipophilic hormones (soluble in lipids but not in water), such as
steroid A steroid is a biologically active organic compound In chemistry Chemistry is the study of the properties and behavior of . It is a that covers the that make up matter to the composed of s, s and s: their composition, structure, ...

steroid
hormones, including testosterone, are transported in water-based blood plasma through specific and non-specific proteins. Specific proteins include sex hormone-binding globulin (SHBG), which binds testosterone,
dihydrotestosterone Dihydrotestosterone (DHT, 5α-dihydrotestosterone, 5α-DHT, androstanolone or stanolone) is an endogenous Endogenous substances and processes are those that originate from within a system such as an organism, Tissue (biology), tissue, or Cell ...
,
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 cycle, estrous and menstrual cycle, menstrual female reproductive cycles. Estradiol is resp ...

estradiol
, and other sex steroids. Non-specific binding proteins include albumin and lipoprotein. The part of the total hormone concentration that is not bound to its respective specific carrier protein is the free part. As a result, testosterone which is not bound to SHBG is called free testosterone. It seems that only the free amount of testosterone can bind to an androgenic receptor, which means they have biological activity.


Steroid hormone activity

The effects of testosterone in humans and other vertebrates occur by way of multiple mechanisms: by activation of the
androgen receptor The androgen receptor (AR), also known as NR3C4 (nuclear receptor subfamily 3, group C, member 4), is a type of nuclear receptor In the field of molecular biology, nuclear receptors are a class of proteins found within cells that are responsi ...

androgen receptor
(directly or as dihydrotestosterone), and by conversion to
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 cycle, estrous and menstrual cycle, menstrual female reproductive cycles. Estradiol is resp ...

estradiol
and activation of certain estrogen receptors. Androgens such as testosterone have also been found to bind to and activate membrane androgen receptors. Testosterone#Free_testosterone, Free testosterone (T) is transported into the cytoplasm of target Tissue (biology), tissue Cell (biology), cells, where it can bind to the
androgen receptor The androgen receptor (AR), also known as NR3C4 (nuclear receptor subfamily 3, group C, member 4), is a type of nuclear receptor In the field of molecular biology, nuclear receptors are a class of proteins found within cells that are responsi ...

androgen receptor
, or can be reduced to Dihydrotestosterone, 5α-dihydrotestosterone (DHT) by the cytoplasmic enzyme 5α-reductase. DHT binds to the same androgen receptor even more strongly than testosterone, so that its androgenic potency is about 5 times that of T. The T-receptor or DHT-receptor complex undergoes a structural change that allows it to move into the cell nucleus and bind directly to specific nucleotide sequences of the chromosome, chromosomal DNA. The areas of binding are called hormone response elements (HREs), and influence transcriptional activity of certain genes, producing the androgen effects. Androgen receptors occur in many different vertebrate body system tissues, and both males and females respond similarly to similar levels. Greatly differing amounts of testosterone prenatally, at puberty, and throughout life account for a share of sexual differentiation, biological differences between males and females. The bones and the brain are two important tissues in humans where the primary effect of testosterone is by way of aromatization to
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 cycle, estrous and menstrual cycle, menstrual female reproductive cycles. Estradiol is resp ...

estradiol
. In the bones, estradiol accelerates ossification of cartilage into bone, leading to closure of the epiphysis, epiphyses and conclusion of growth. In the central nervous system, testosterone is aromatized to estradiol. Estradiol rather than testosterone serves as the most important feedback signal to the hypothalamus (especially affecting luteinizing hormone, LH secretion). In many mammals, prenatal or perinatal "masculinization" of the sexual dimorphism, sexually dimorphic areas of the brain by estradiol derived from testosterone programs later male sexual behavior.


Neurosteroid activity

Testosterone, via its active metabolite 3α-androstanediol, is a potent positive allosteric modulator of the GABAA receptor, GABAA receptor. Testosterone has been found to act as an receptor antagonist, antagonist of the TrkA and p75NTR, p75NTR, receptor (biochemistry), receptors for the neurotrophin nerve growth factor (NGF), with high affinity (pharmacology), affinity (around 5 nM). In contrast to testosterone, DHEA and DHEA sulfate have been found to act as high-affinity agonists of these receptors. Testosterone is an antagonist of the sigma receptor, sigma sigma-1 receptor, σ1 receptor (Ki = 1,014 or 201 nM). However, the concentrations of testosterone required for binding the receptor are far above even total circulating concentrations of testosterone in adult males (which range between 10 and 35 nM).


Biochemistry


Biosynthesis

Like other
steroid A steroid is a biologically active organic compound In chemistry Chemistry is the study of the properties and behavior of . It is a that covers the that make up matter to the composed of s, s and s: their composition, structure, ...

steroid
hormones, testosterone is derived from cholesterol (see figure). The first step in the biosynthesis involves the oxidative cleavage of the side-chain of cholesterol by cholesterol side-chain cleavage enzyme (P450scc, CYP11A1), a mitochondrion, mitochondrial cytochrome P450 oxidase with the loss of six carbon atoms to give pregnenolone. In the next step, two additional carbon atoms are removed by the CYP17A1 (17α-hydroxylase/17,20-lyase) enzyme in the endoplasmic reticulum to yield a variety of C19 steroids. In addition, the 3β-hydroxyl group is oxidized by 3β-hydroxysteroid dehydrogenase to produce androstenedione. In the final and rate limiting step, the C17 keto group androstenedione is reduced by 17β-hydroxysteroid dehydrogenase to yield testosterone. The largest amounts of testosterone (>95%) are produced by the testis, testes in men, while the adrenal glands account for most of the remainder. Testosterone is also synthesized in far smaller total quantities in women by the adrenal glands, theca of follicle, thecal cells of the ovary, ovaries, and, during pregnancy, by the placenta. In the testes, testosterone is produced by the Leydig cells. The male generative glands also contain
Sertoli cell A Sertoli cell (a kind of sustentacular cell A sustentacular cell is a type of cell primarily associated with structural support, they can be found in various tissues. * Sustentacular cells of the olfactory epithelium The olfactory epithelium ...
s, which require testosterone for spermatogenesis. Like most hormones, testosterone is supplied to target tissues in the blood where much of it is transported bound to a specific plasma protein, sex hormone-binding globulin (SHBG).


Regulation

In males, testosterone is synthesized primarily in Leydig cells. The number of Leydig cells in turn is regulated by luteinizing hormone (LH) and follicle-stimulating hormone (FSH). In addition, the amount of testosterone produced by existing Leydig cells is under the control of LH, which regulates the expression of 17β-hydroxysteroid dehydrogenase. The amount of testosterone synthesized is regulated by the hypothalamic–pituitary–gonadal axis, hypothalamic–pituitary–testicular axis (see figure to the right). When testosterone levels are low, gonadotropin-releasing hormone (gonadotropin-releasing hormone, GnRH) is released by the
hypothalamus The hypothalamus (from Ancient Greek wikt:ὑπό, ὑπό, "under", and wikt:θάλαμος, θάλαμος, "chamber") is a portion of the brain that contains a number of small Nucleus (neuroanatomy), nuclei with a variety of functions. One of ...

hypothalamus
, which in turn stimulates the pituitary gland to release FSH and LH. These latter two hormones stimulate the testis to synthesize testosterone. Finally, increasing levels of testosterone through a negative feedback loop act on the hypothalamus and pituitary to inhibit the release of GnRH and FSH/LH, respectively. Factors affecting testosterone levels may include: * Age: Testosterone levels gradually reduce as men age. This effect is sometimes referred to as andropause or late-onset hypogonadism. * Exercise: Strength training, Resistance training increases testosterone levels, however, in older men, that increase can be avoided by protein ingestion. Endurance training in men may lead to lower testosterone levels. * Nutrients: Vitamin A deficiency may lead to sub-optimal plasma testosterone levels. The secosteroid vitamin D in levels of 400–1000 international unit, IU/d (10–25 µg/d) raises testosterone levels. Zinc deficiency lowers testosterone levels but over-supplementation has no effect on serum testosterone. There is limited evidence that low-fat diets may reduce total and free testosterone levels in men. * Weight loss: Reduction in weight may result in an increase in testosterone levels. Fat cells synthesize the enzyme aromatase, which converts testosterone, the male sex hormone, into estradiol, the female sex hormone. However no clear association between body mass index and testosterone levels has been found. * Miscellaneous: ''Sleep'': (REM sleep) increases nocturnal testosterone levels. ''Behavior'': Dominance challenges can, in some cases, stimulate increased testosterone release in men. ''Drugs'': Natural or man-made antiandrogens including spearmint tea reduce testosterone levels. Licorice can decrease the production of testosterone and this effect is greater in females.


Distribution

The plasma protein binding of testosterone is 98.0 to 98.5%, with 1.5 to 2.0% free or unbound. It is bound 65% to sex hormone-binding globulin (SHBG) and 33% bound weakly to human serum albumin, albumin.


Metabolism

Both testosterone and 5α-DHT are metabolism, metabolized mainly in the liver. Approximately 50% of testosterone is metabolized via conjugation (biochemistry), conjugation into testosterone glucuronide and to a lesser extent testosterone sulfate by glucuronosyltransferases and sulfotransferases, respectively. An additional 40% of testosterone is metabolized in equal proportions into the 17-ketosteroids androsterone and etiocholanolone via the combined actions of 5α-reductase, 5α- and 5β-reductases, 3α-hydroxysteroid dehydrogenase, and 17β-HSD, in that order. Androsterone and etiocholanolone are then glucuronidation, glucuronidated and to a lesser extent sulfation, sulfated similarly to testosterone. The conjugates of testosterone and its hepatic metabolites are released from the liver into circulatory system, circulation and excretion, excreted in the urine and bile. Only a small fraction (2%) of testosterone is excreted unchanged in the urine. In the hepatic 17-ketosteroid pathway of testosterone metabolism, testosterone is converted in the liver by 5α-reductase and 5β-reductase into 5α-DHT and the inactive 5β-Dihydrotestosterone, 5β-DHT, respectively. Then, 5α-DHT and 5β-DHT are converted by 3α-HSD into 3α-androstanediol and 3α-etiocholanediol, respectively. Subsequently, 3α-androstanediol and 3α-etiocholanediol are converted by 17β-HSD into androsterone and etiocholanolone, which is followed by their conjugation and excretion. 3β-Androstanediol and 3β-etiocholanediol can also be formed in this pathway when 5α-DHT and 5β-DHT are acted upon by 3β-HSD instead of 3α-HSD, respectively, and they can then be transformed into epiandrosterone and epietiocholanolone, respectively. A small portion of approximately 3% of testosterone is reversible reaction, reversibly converted in the liver into androstenedione by 17β-HSD. In addition to conjugation and the 17-ketosteroid pathway, testosterone can also be hydroxylation, hydroxylated and oxidation, oxidized in the liver by cytochrome P450
enzyme Enzymes () are proteins that act as biological catalysts (biocatalysts). Catalysts accelerate chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates in ...

enzyme
s, including CYP3A4, CYP3A5, CYP2C9, CYP2C19, and CYP2D6. 6β-Hydroxylation and to a lesser extent 16β-hydroxylation are the major transformations. The 6β-hydroxylation of testosterone is catalyzed mainly by CYP3A4 and to a lesser extent CYP3A5 and is responsible for 75 to 80% of cytochrome P450-mediated testosterone metabolism. In addition to 6β- and 16β-hydroxytestosterone, 1β-, 2α/β-, 11β-, and 15β-hydroxytestosterone are also formed as minor metabolites. Certain cytochrome P450 enzymes such as CYP2C9 and CYP2C19 can also oxidize testosterone at the C17 position to form androstenedione. Two of the immediate metabolites of testosterone, 5α-DHT 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 cycle, estrous and menstrual cycle, menstrual female reproductive cycles. Estradiol is resp ...

estradiol
, are biologically important and can be formed both in the liver and in extrahepatic tissues. Approximately 5 to 7% of testosterone is converted by 5α-reductase into 5α-DHT, with circulating levels of 5α-DHT about 10% of those of testosterone, and approximately 0.3% of testosterone is converted into estradiol by
aromatase Aromatase, also called estrogen synthetase or estrogen synthase, is an enzyme Enzymes () are proteins that act as biological catalysts (biocatalysts). Catalysts accelerate chemical reactions. The molecules upon which enzymes may act are cal ...
. 5α-Reductase is highly expressed in the male reproductive system, male reproductive organs (including the prostate gland,
seminal vesicle The seminal vesicles (also called vesicular glands, or seminal glands) are a pair of two convoluted tubular glands that lie behind the urinary bladder The urinary bladder, or simply bladder, is a hollow muscular MUSCULAR (DS-200B), located i ...
s, and epididymides), skin, hair follicles, and brain and aromatase is highly expressed in adipose tissue,
bone A bone is a rigid tissue Tissue may refer to: Biology * Tissue (biology), an ensemble of similar cells that together carry out a specific function * ''Triphosa haesitata'', a species of geometer moth found in North America * ''Triphosa dubit ...

bone
, and the brain. As much as 90% of testosterone is converted into 5α-DHT in so-called androgenic tissues with high 5α-reductase expression, and due to the several-fold greater potency of 5α-DHT as an AR agonist relative to testosterone, it has been estimated that the effects of testosterone are potentiated 2- to 3-fold in such tissues.


Levels

Total levels of testosterone in the body have been reported as 264 to 916 ng/dL (nanograms per deciliter) in non-obese European and American men age 19 to 39 years, while mean testosterone levels in adult men have been reported as 630 ng/dL. Although commonly used as a reference range, some physicians have disputed the use of this range to determine
hypogonadism Hypogonadism means diminished functional activity of the gonad A gonad, sex gland, or reproductive gland is a mixed gland that produces the gametes (sex cells) and sex hormones of an organism. In the female of the species the reproductive cell ...
. Several professional medical groups have recommended that 350 ng/dl generally be considered the minimum normal level, which is consistent with previous findings. Levels of testosterone in men decline with age. In women, mean levels of total testosterone have been reported to be 32.6 ng/dL. In women with hyperandrogenism, mean levels of total testosterone have been reported to be 62.1 ng/dL.


Measurement

Testosterone's bioavailable concentration is commonly determined using the Vermeulen calculation or more precisely using the modified Vermeulen method, which considers the dimeric form of sex-hormone-binding-globulin. Both methods use chemical equilibrium to derive the concentration of bioavailable testosterone: in circulation, testosterone has two major binding partners, albumin (weakly bound) and sex-hormone-binding-globulin (strongly bound). These methods are described in detail in the accompanying figure. File:Dimeric SHBG.png, Dimeric sex-hormone-binding-globulin with its testosterone ligands File:Method for determining testosterone.png, Two methods for determining the concentration of bioavailable testosterone.


History

A testicular action was linked to circulating blood fractions – now understood to be a family of androgenic hormones – in the early work on castration and testicular transplantation in fowl by Arnold Adolph Berthold (1803–1861). Research on the action of testosterone received a brief boost in 1889, when the Harvard professor Charles-Édouard Brown-Séquard (1817–1894), then in Paris, self-injected subcutaneously a "rejuvenating elixir" consisting of an extract of dog and guinea pig testicle. He reported in ''The Lancet'' that his vigor and feeling of well-being were markedly restored but the effects were transient, and Brown-Séquard's hopes for the compound were dashed. Suffering the ridicule of his colleagues, he abandoned his work on the mechanisms and effects of androgens in human beings. In 1927, the University of Chicago's Professor of Physiologic Chemistry, Fred C. Koch, established easy access to a large source of bovine testicles — the Chicago stockyards — and recruited students willing to endure the tedious work of extracting their isolates. In that year, Koch and his student, Lemuel McGee, derived 20 mg of a substance from a supply of 40 pounds of bovine testicles that, when administered to castrated roosters, pigs and rats, re-masculinized them. The group of Ernst Laqueur at the University of Amsterdam purified testosterone from bovine testicles in a similar manner in 1934, but the isolation of the hormone from animal tissues in amounts permitting serious study in humans was not feasible until three European pharmaceutical giants—Schering AG, Schering (Berlin, Germany), Organon International, Organon (Oss, Netherlands) and Novartis, Ciba (Basel, Switzerland)—began full-scale steroid research and development programs in the 1930s. The Organon group in the Netherlands were the first to isolate the hormone, identified in a May 1935 paper "On Crystalline Male Hormone from Testicles (Testosterone)". They named the hormone ''testosterone'', from the stem (linguistics), stems of ''testicle'' and ''sterol'', and the suffix of ''ketone''. The structure was worked out by Schering's Adolf Butenandt, at the Faculty of Chemistry, Gdańsk University of Technology, ''Chemisches Institut'' of Gdańsk University of Technology, Technical University in Gdańsk. The chemical synthesis of testosterone from cholesterol was achieved in August that year by Butenandt and Hanisch. Only a week later, the Ciba group in Zurich, Leopold Ruzicka (1887–1976) and A. Wettstein, published their synthesis of testosterone. These independent partial syntheses of testosterone from a cholesterol base earned both Butenandt and Ruzicka the joint 1939 Nobel Prize in Chemistry. Testosterone was identified as 17β-hydroxyandrost-4-en-3-one (C19H28O2), a solid polycyclic alcohol with a hydroxyl group at the 17th carbon atom. This also made it obvious that additional modifications on the synthesized testosterone could be made, i.e., esterification and alkylation. The partial synthesis in the 1930s of abundant, potent testosterone esters permitted the characterization of the hormone's effects, so that Kochakian and Murlin (1936) were able to show that testosterone raised nitrogen retention (a mechanism central to anabolism) in the dog, after which Allan Kenyon's group was able to demonstrate both anabolic and androgenic effects of testosterone propionate in eunuchoidal men, boys, and women. The period of the early 1930s to the 1950s has been called "The Golden Age of Steroid Chemistry", and work during this period progressed quickly.


Other species

Testosterone is observed in most vertebrates. Testosterone and the classical nuclear
androgen receptor The androgen receptor (AR), also known as NR3C4 (nuclear receptor subfamily 3, group C, member 4), is a type of nuclear receptor In the field of molecular biology, nuclear receptors are a class of proteins found within cells that are responsi ...

androgen receptor
first appeared in gnathostomes (jawed vertebrates). Agnathans (jawless vertebrates) such as lampreys do not produce testosterone but instead use androstenedione as a male sex hormone. Fish make a slightly different form called 11-ketotestosterone. Its counterpart in insects is ecdysone. The presence of these ubiquitous steroids in a wide range of animals suggest that
sex hormone Sex hormones, also known as sex steroids, gonadocorticoids and gonadal steroids, are steroid hormone A steroid hormone is a steroid , hypothetical a steroid with 32 carbon atoms. Its core ring system (ABCD), composed of 17 carbon atoms, is ...
s have an ancient evolutionary history.


See also

* List of androgens/anabolic steroids * List of human hormones


References


Further reading

* * * {{Authority control Testosterone, Cyclopentanols Alkene derivatives Androgens and anabolic steroids Androstanes Estrogens GABAA receptor positive allosteric modulators Hormones of the testis Hormones of the ovary Hormones of the hypothalamus-pituitary-gonad axis Hormones of the suprarenal cortex Enones Neuroendocrinology Human hormones Sex hormones