An androgen (from Greek andr-, the stem of the word meaning ) is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in by binding to androgen receptors.
Androgens increase in both males and females during puberty.
Although androgens are commonly thought of only as male Sex steroids, females also have them, but at lower levels: they function in libido and sexual arousal. Androgens are the precursors to in both men and women.
In addition to their role as natural hormones, androgens are used as ; for information on androgens as medications, see the androgen replacement therapy and anabolic steroid articles.
Types and examples
The main subset of androgens, known as adrenal androgens, is composed of 19-carbon steroids synthesized in the
zona reticularis, the innermost layer of the
adrenal cortex. Adrenal androgens function as weak steroids (though some are precursors), and the subset includes dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA-S),
androstenedione (A4), and
androstenediol (A5).
Besides testosterone, other androgens include:
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Dehydroepiandrosterone (DHEA) is a steroid hormone produced in the adrenal cortex from cholesterol.
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Androstenedione (A4) is an androgenic steroid produced by the testes, adrenal cortex, and ovaries. While androstenedione is converted metabolically to testosterone and other androgens, it is also the parent structure of estrone. Use of androstenedione as an athletic or bodybuilding supplement has been banned by the International Olympic Committee, as well as other sporting organizations.
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Androstenediol (A5) is a steroid metabolite of DHEA and the precursor to sex hormones testosterone and estradiol.
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Androsterone is a chemical byproduct created during the breakdown of androgens, or derived from progesterone, that also exerts minor masculinising effects, but with one-seventh the intensity of testosterone. It is found in approximately equal amounts in the blood plasma and urine of both males and females.
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Dihydrotestosterone (DHT) is a metabolite of testosterone, and a more potent androgen than testosterone in that it binds more strongly to androgen receptors. It is produced in the skin and reproductive tissue.
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A4 and testosterone can also have an extra hydroxyl (-OH) or ketone (=O) group bound on position 11. In this case you can have 11-hydroxyandrostenedione, 11-ketoandrostenedione, 11-hydroxytestosterone, and 11-ketotestosterone. The latter has the same biological activity as testosterone
Determined by consideration of all biological assay methods ():
Female ovarian and adrenal androgens
The ovaries and adrenal glands also produce androgens, but at much lower levels than the testes. Regarding the relative contributions of ovaries and adrenal glands to female androgen levels, in a study with six menstruating women the following observations have been made:
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Adrenal contribution to peripheral T, DHT, A, DHEA and DHEA-S is relatively constant throughout the menstrual cycle.
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Ovarian contribution of peripheral T, A and DHEA-S reaches maximum levels at mid-cycle, whereas ovarian contribution to peripheral DHT and DHEA does not seem to be influenced by the menstrual cycle.
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Ovary and adrenal cortex contribute equally to peripheral T, DHT and A, with the exception that at mid-cycle ovarian contribution of peripheral A is twice that of the adrenal.
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Peripheral DHEA and DHEA-S are produced mainly in the adrenal cortex which provides 80% of DHEA and over 90% of DHEA-S.
+ Ovarian and adrenal contribution to peripheral androgens during the menstrual cycle | Adrenal (%) |
| 80 |
| 90–96 |
| 30–55 |
| 40–66 |
| 50 |
| F = early follicular, M = midcycle, L = late luteal phase. |
Biological function
Male prenatal development
Testes formation
During mammalian development, the gonads are at first capable of becoming either
ovary or testes.
In humans, starting at about week 4, the gonadal rudiments are present within the intermediate mesoderm adjacent to the developing kidneys. At about week 6, epithelial
sex cords develop within the forming testes and incorporate the
as they migrate into the gonads. In males, certain
Y chromosome genes, particularly
SRY, control development of the male phenotype, including conversion of the early bipotential gonad into testes. In males, the sex cords fully invade the developing gonads.
Androgen production
The mesoderm-derived
Epithelium cells of the sex cords in developing testes become the
, which will function to support sperm cell formation. A minor population of nonepithelial cells appear between the tubules by week 8 of human fetal development. These are
. Soon after they differentiate, Leydig cells begin to produce androgens.
Androgen effects
The androgens function as paracrine
required by the Sertoli cells to support sperm production. They are also required for the masculinization of the developing male fetus (including penis and scrotum formation). Under the influence of androgens, remnants of the
mesonephron, the
Wolffian ducts, develop into the
epididymis,
vas deferens and
seminal vesicles. This action of androgens is supported by a hormone from Sertoli cells, Müllerian inhibitory hormone (MIH), which prevents the embryonic Müllerian ducts from developing into fallopian tubes and other female reproductive tract tissues in male embryos. MIH and androgens cooperate to allow for movement of testes into the scrotum.
Early regulation
Before the production of the pituitary hormone luteinizing hormone (LH) by the embryo starting at about weeks 11–12, human chorionic gonadotrophin (hCG) promotes the differentiation of Leydig cells and their production of androgens at week 8. Androgen action in target tissues often involves conversion of testosterone to 5α-dihydrotestosterone (DHT).
Male pubertal development
At the time of
puberty, androgen levels increase dramatically in males, and androgens mediate the development of masculine secondary sexual characteristics as well as the activation of
spermatogenesis and
fertility and masculine behavioral changes such as increased
sex drive. Masculine secondary sexual characteristics include
androgenic hair,
voice deepening, emergence of the Adam's apple, broadening of the shoulders, increased
muscle mass, and
penile growth.
Spermatogenesis
During puberty, androgen, LH and follicle stimulating hormone (FSH) production increase and the sex cords hollow out, forming the seminiferous tubules, and the germ cells start to differentiate into sperm. Throughout adulthood, androgens and FSH cooperatively act on Sertoli cells in the testes to support sperm production.
Exogenous androgen supplements can be used as a male contraceptive. Elevated androgen levels caused by use of androgen supplements can inhibit production of LH and block production of endogenous androgens by Leydig cells. Without the locally high levels of androgens in testes due to androgen production by Leydig cells, the seminiferous tubules can degenerate, resulting in infertility. For this reason, many transdermal androgen patches are applied to the scrotum.
Fat deposition
Males typically have less body fat than females. Recent results indicate androgens inhibit the ability of some fat cells to store lipids by blocking a signal transduction pathway that normally supports adipocyte function.
Also, androgens, but not estrogens, increase beta adrenergic receptors while decreasing alpha adrenergic receptors—which results in increased levels of epinephrine/norepinephrine due to lack of alpha-2 receptor negative feedback and decreased fat accumulation due to epinephrine/norepinephrine then acting on lipolysis-inducing beta receptors.
Muscle mass
Males typically have more
skeletal muscle mass than females. Androgens promote the enlargement of skeletal muscle cells in a coordinated manner by acting on several cell types in skeletal muscle tissue.
One cell type, called the
Muscle cell, conveys androgen receptors for generating muscle. Fusion of myoblasts generates
, in a process linked to androgen receptor levels.
Higher androgen levels lead to increased expression of androgen receptor.
Brain
Circulating levels of androgens can influence human behavior because some
are sensitive to steroid hormones. Androgen levels have been implicated in the regulation of human
aggression and libido. Indeed, androgens are capable of altering the structure of the brain in several species, including mice, rats, and primates, producing
sex differences.
More recent studies showing the general mood of
transgender men, who have undergone transgender hormone replacement therapy replacing
with androgens, do not show any substantial long-term
behavioral changes.
Numerous reports have shown androgens alone are capable of altering the structure of the brain,
Evidence from neurogenesis (formation of new neurons) studies on male rats has shown that the hippocampus is a useful brain region to examine when determining the effects of androgens on behavior. To examine neurogenesis, wild-type male rats were compared with male rats that had androgen insensitivity syndrome, a genetic difference resulting in complete or partial insensitivity to androgens and a lack of external male genitalia.
Neural injections of bromodeoxyuridine (BrdU) were applied to males of both groups to test for neurogenesis. Analysis showed that testosterone and dihydrotestosterone regulated adult hippocampal neurogenesis (AHN). Adult hippocampal neurogenesis was regulated through the androgen receptor in the wild-type male rats, but not in the TMF male rats. To further test the role of activated androgen receptors on AHN, flutamide, an antiandrogen drug that competes with testosterone and dihydrotestosterone for androgen receptors, and dihydrotestosterone were administered to normal male rats. Dihydrotestosterone increased the number of BrdU cells, while flutamide inhibited these cells. Moreover, estrogens had no effect. This research demonstrates how androgens can increase AHN.
Researchers also examined how mild exercise affected androgen synthesis which in turn causes AHN activation of N-methyl--aspartate (NMDA) receptors. NMDA induces a calcium flux that allows for synaptic plasticity which is crucial for AHN.
Researchers injected both orchidectomized (ORX) (castrated) and sham castrated male rats with BrdU to determine if the number of new cells was increased. They found that AHN in male rats is increased with mild exercise by boosting synthesis of dihydrotestosterone in the hippocampus. Again it was noted that AHN was not increased via activation of the estrogen receptors.
Androgen regulation decreases the likelihood of depression in males. In preadolescent male rats, neonatal rats treated with flutamide developed more depression-like symptoms compared to control rats.
Again BrdU was injected into both groups of rats in order to see if cells were multiplying in the living tissue. These results demonstrate how the organization of androgens has a positive effect on preadolescent hippocampal neurogenesis that may be linked with lower depression-like symptoms.
Social isolation has a hindering effect in AHN whereas normal regulation of androgens increases AHN. A study using male rats showed that testosterone may block social isolation, which results in hippocampal neurogenesis reaching homeostasis—regulation that keeps internal conditions stable. A BrdU analysis showed that excess testosterone did not increase this blocking effect against social isolation; that is, the natural circulating levels of androgens cancel out the negative effects of social isolation on AHN.
Female-specific effects
Androgens have potential roles in relaxation of the
myometrium via non-genomic, androgen receptor-independent pathways, preventing premature uterine contractions in pregnancy.
Androgen insensitivity
Reduced ability of an
sex chromosome-
karyotype fetus to respond to androgens can result in one of several conditions, including infertility and several forms of
intersex conditions.
Miscellaneous
Yolk androgen levels in certain birds have been positively correlated to social dominance later in life. See
American coot.
Biological activity
Androgens bind to and activate androgen receptors (ARs) to mediate most of their biological effects.
Relative potency
Determined by consideration of all biological assay methods ():
5α-Dihydrotestosterone (DHT) was 2.4 times more potent than testosterone at maintaining normal prostate weight and duct lumen mass (this is a measure of epithelial cell function stimulation). Whereas DHT was equally potent as testosterone at preventing prostate cell death after castration.
Non-genomic actions
Androgens have also been found to signal through membrane androgen receptors, which are distinct from the classical nuclear androgen receptor.
Biochemistry
Biosynthesis
Androgens are
biosynthesis from
cholesterol and are produced primarily in the
(testicles and ovaries) and also in the
. The testicles produce a much higher quantity than the ovaries. Conversion of testosterone to the more potent DHT occurs in
prostate gland,
liver,
brain and skin.
Metabolism
Androgens are
metabolism mainly in the
liver.
Medical uses
A low testosterone level (hypogonadism) in men may be treated with testosterone administration. Prostate cancer may be treated by removing the major source of testosterone: testicle removal (
orchiectomy); or agents which block androgens from accessing their receptor:
.
See also
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Androgen insensitivity syndrome
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Androgen insufficiency syndrome
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Andrology
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Endocrine system
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Exercise and androgen levels
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List of androgens/anabolic steroids
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List of androgens/anabolic steroids available in the United States
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List of steroid abbreviations
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Testosterone and the cardiovascular system
