Androgen

Androgen
G03B
Biological target	Androgen receptor, mARs (e.g., GPRC6A, others)
External links
MeSH	D000728
Legal status
In Wikidata

An androgen (from Greek andr-, the stem of the word meaning "man") is any natural or synthetic

.

Androgens increase in both males and females during puberty.^[3] The major androgen in males is testosterone.^[4] Dihydrotestosterone (DHT) and androstenedione are of equal importance in male development.^[4] DHT in utero causes differentiation of the penis, scrotum and prostate. In adulthood, DHT contributes to balding, prostate growth, and sebaceous gland activity.

Although androgens are commonly thought of only as male

in both men and women.

In addition to their role as natural hormones, androgens are used as medications; 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:

• Dehydroepiandrosterone (DHEA) is a steroid hormone produced in the adrenal cortex from cholesterol.^[5] It is the primary precursor of both the androgen and estrogen sex hormones. DHEA is also called dehydroisoandrosterone or dehydroandrosterone.
• Androstenedione (A4) is an androgenic steroid produced by the
  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.
• Androstenediol (A5) is a steroid metabolite of DHEA and the precursor to sex hormones testosterone and estradiol.
• 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 plasma and urine of both males and females.
• 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.
• A4 and testosterone can also have an extra hydroxyl (-OH) or keton (=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^[6] and, therefore, these are also very important in healthy individals and patients with diseases like, congenital adrenal hyperplasia, polycystic ovarian syndrome, or premature adrenarche.^[6]

Determined by consideration of all biological assay methods (c. 1970):^[7]

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:^[8]

• Adrenal contribution to peripheral T, DHT, A, DHEA and DHEA-S is relatively constant throughout the menstrual cycle.
• 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.
• 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.
• 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^[8]

Androgen	Ovarian (%) (F, M, L)	Adrenal (%)
DHEA	20	80
DHEA-S	4, 10, 4	90–96
Androstenedione	45, 70, 60	30–55
Testosterone	33, 60, 33	40–66
DHT	50	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

, 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 epithelial cells of the sex cords in developing testes become the Sertoli cells, 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 Leydig cells. Soon after they differentiate, Leydig cells begin to produce androgens.

Androgen effects

The androgens function as

. 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

(DHT).

Male pubertal development

At the time of

penile growth

.

Spermatogenesis

During puberty, androgen, LH and

. 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.[11] 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

.

Brain

Circulating levels of androgens can influence human behavior because some

Numerous reports have shown androgens alone are capable of altering the

but identification of which alterations in neuroanatomy stem from androgens or estrogens is difficult, because of their potential for conversion.

Evidence from

male genitalia

.

Neural injections of

inhibited these cells.

Moreover, estrogens had no effect. This research demonstrates how androgens can increase AHN.[19]

Researchers also examined how mild exercise affected androgen synthesis which in turn causes AHN activation of

receptors.

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

.

Again it was noted that AHN was not increased via activation of the estrogen receptors.^[20]

Androgen regulation decreases the likelihood of

compared to control rats.

Again

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.^[23]

Androgen insensitivity

Reduced ability of an XY-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

.

Relative potency

Determined by consideration of all biological assay methods (c. 1970):^[7]

Androgen	Potency (%)
Testosterone	40
5α-Dihydrotestosterone (DHT)	100
Androstenediol	.0008
Androstenedione	.04
Dehydroepiandrosterone	.02
Androsterone	.06

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.^[24] One of the 11-oxygenated androgens, namely 11-ketotestosterone, has the same potency as testosterone. ^[25]

Non-genomic actions

Androgens have also been found to signal through membrane androgen receptors, which are distinct from the classical nuclear androgen receptor.^[26][27][28]

Biochemistry

estrogens

.

Biosynthesis

Androgens are

and skin.

• v
• t
• e

Production rates, secretion rates, clearance rates, and blood levels of major sex hormones

Sex	Sex hormone	Reproductive phase	Blood production rate	Gonadal secretion rate	Metabolic clearance rate	Reference range (serum levels)
						SI units	Non-SI units
Men	Androstenedione	–	2.8 mg/day	1.6 mg/day	2200 L/day	2.8–7.3 nmol/L	80–210 ng/dL
	Testosterone	–	6.5 mg/day	6.2 mg/day	950 L/day	6.9–34.7 nmol/L	200–1000 ng/dL
	Estrone	–	150 μg/day	110 μg/day	2050 L/day	37–250 pmol/L	10–70 pg/mL
	Estradiol	–	60 μg/day	50 μg/day	1600 L/day	<37–210 pmol/L	10–57 pg/mL
	Estrone sulfate	–	80 μg/day	Insignificant	167 L/day	600–2500 pmol/L	200–900 pg/mL
Women	Androstenedione	–	3.2 mg/day	2.8 mg/day	2000 L/day	3.1–12.2 nmol/L	89–350 ng/dL
	Testosterone	–	190 μg/day	60 μg/day	500 L/day	0.7–2.8 nmol/L	20–81 ng/dL
	Estrone	Follicular phase	110 μg/day	80 μg/day	2200 L/day	110–400 pmol/L	30–110 pg/mL
		Luteal phase	260 μg/day	150 μg/day	2200 L/day	310–660 pmol/L	80–180 pg/mL
		Postmenopause	40 μg/day	Insignificant	1610 L/day	22–230 pmol/L	6–60 pg/mL
	Estradiol	Follicular phase	90 μg/day	80 μg/day	1200 L/day	<37–360 pmol/L	10–98 pg/mL
		Luteal phase	250 μg/day	240 μg/day	1200 L/day	699–1250 pmol/L	190–341 pg/mL
		Postmenopause	6 μg/day	Insignificant	910 L/day	<37–140 pmol/L	10–38 pg/mL
	Estrone sulfate	Follicular phase	100 μg/day	Insignificant	146 L/day	700–3600 pmol/L	250–1300 pg/mL
		Luteal phase	180 μg/day	Insignificant	146 L/day	1100–7300 pmol/L	400–2600 pg/mL
	Progesterone	Follicular phase	2 mg/day	1.7 mg/day	2100 L/day	0.3–3 nmol/L	0.1–0.9 ng/mL
		Luteal phase	25 mg/day	24 mg/day	2100 L/day	19–45 nmol/L	6–14 ng/mL
Notes and sources Notes: "The concentration of a steroid in the circulation is determined by the rate at which it is secreted from glands, the rate of metabolism of precursor or prehormones into the steroid, and the rate at which it is extracted by tissues and metabolized. The secretion rate of a steroid refers to the total secretion of the compound from a gland per unit time. Secretion rates have been assessed by sampling the venous effluent from a gland over time and subtracting out the arterial and peripheral venous hormone concentration. The metabolic clearance rate of a steroid is defined as the volume of blood that has been completely cleared of the hormone per unit time. The production rate of a steroid hormone refers to entry into the blood of the compound from all possible sources, including secretion from glands and conversion of prohormones into the steroid of interest. At steady state, the amount of hormone entering the blood from all sources will be equal to the rate at which it is being cleared (metabolic clearance rate) multiplied by blood concentration (production rate = metabolic clearance rate × concentration). If there is little contribution of prohormone metabolism to the circulating pool of steroid, then the production rate will approximate the secretion rate." Sources: See template.

Metabolism

Androgens are metabolized 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: antiandrogens.

See also

References