Androgen
Androgen is the generic term for any natural or synthetic compound, usually a
steroid hormone, that stimulates or controls the development and maintenance of masculine characteristics in
vertebrates by binding to
androgen receptors. This includes the activity of the accessory
male sex organs and development of male
secondary sex characteristics. Androgens, which were first discovered in
1936, are also called
androgenic hormones or
testoids. Androgens are also the original
anabolic steroids. They are also the precursor of all
estrogens, the
female sex hormones. The primary and most well-known androgen is
testosterone.
A subset of androgens,
adrenal androgens, includes any of the 19-carbon steroids synthesized by the
adrenal cortex, the outer portion of the
adrenal gland, that function as weak steroids or steroid precursors, including
dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA-S), and androstenedione.
Besides testosterone, other androgens include:
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Dehydroepiandrosterone (DHEA): a steroid hormone produced from
cholesterol in the adrenal cortex, which is the primary precursor of natural estrogens. DHEA is also called dehydroisoandrosterone or dehydroandrosterone.
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Androstenedione (Andro): an androgenic steroid, which is produced by the
testes, adrenal cortex, and
ovaries. While androstenediones are converted metabolically to testosterone and other androgens, they are also the parent structure of
estrone. Use of androstenedione as an athletic or body building
supplement has been banned by the
International Olympic Committee as well as other sporting organizations.
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Androstanediol: the steroid
metabolite that is thought to act as the main regulator of
gonadotropin secretion.
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Androsterone: a chemical by-product 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.
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Dihydrotestosterone (DHT): a
metabolite of testosterone that is actually a more potent androgen in that it binds more strongly to androgen receptors.
Development of the male
During mammalian development, the gonads are at first capable of becoming either
ovaries or testes
[Online textbook: "Developmental Biology" 6th ed. By Scott F. Gilbert (2000) published by Sinauer Associates, Inc. of Sunderland (MA).]. In humans, starting at about week 4 the gonadal rudiments are present within
intermediate mesoderm adjacent to the developing kidneys. At about week 6, epithelial
sex cords develop within the forming testes and incorporate the
germ cells 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.
By week 8 of human fetal development, Leydig cells appear in the differentiating gonads of males. 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 non-epithelial cells exists between the tubules, these are the androgen-producing Leydig cells. The Leydig cells can be viewed as producers of androgens that function as
paracrine hormones required by the Sertoli cells in order to support sperm production. Soon after they differentiate, Leydig cells begin to produce androgens which are required for 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,
AMH, which prevents the embryonic Müllerian ducts from developing into fallopian tubes and other female reproductive tract tissues in male embryos. AMH and androgens cooperate to allow for the normal movement of testes into the scrotum.
Before the production of the pituitary 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. Androgen action in target tissues often involves conversion of testosterone to 5α-dihydrotestosterone (
DHT).
Spermatogenesis
During puberty, androgen,
LH and
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
[Online textbook: "Endocrinology: An Integrated Approach" by S. S. Nussey and S. A. Whitehead (2001) published by BIOS Scientific Publishers, Ltd; Oxford, UK.]. 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.
Inhibition of fat deposition
Males typically have less
adipose tissue than females. Recent results indicate that androgens inhibit the ability of some fat cells to store lipids by blocking a signal transduction pathway that normally supports adipocyte function
[Full text article available in PDF format: "Testosterone Inhibits Adipogenic Differentiation in 3T3-L1 Cells: Nuclear Translocation of Androgen Receptor Complex with {beta}-Catenin and TCF4 may Bypass Canonical Wnt Signaling to Downregulate Adipogenic Transcription Factors" by R. Singh, J. N. Artaza, W. E. Taylor, M. Braga, X. Yuan, N. F. Gonzalez-Cadavid and S Bhasin in Endocrinology (2005) ].
Muscle mass
Males typically have more
skeletal muscle mass than females. Androgens promote the enlargement of skeletal muscle cells and probably act in a coordinated manner to enhance muscle function by acting on several cell types in skeletal muscle tissue
[Androgen Receptor in Human Skeletal Muscle and Cultured Muscle Satellite Cells: Up-Regulation by Androgen Treatment by Indrani Sinha-Hikim, Wayne E. Taylor, Nestor F. Gonzalez-Cadavid, Wei Zheng and Shalender Bhasin in The Journal of Clinical Endocrinology & Metabolism (2004 ) volume 89 pages 5245-5255.].
Brain
Circulating levels of androgens can influence human behavior because some
neurons are sensitive to steroid hormones. Androgen levels have been implicated in the regulation of human
aggression[Full text article available in PDF format: "Testosterone and aggressiveness" by Marco Giammanco, Garden Tabacchi, Santo Giammanco, Danila Di Majo and Maurizio La Guardia in Endocrinology (2005) ] and libido.
Reduced ability of a
XY karyotype fetus to respond to androgens can result in one of several problems, including infertility and several forms of
intersex conditions. See
androgen insensitivity syndrome (AIS).
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andrology*
antiandrogen
