Drugs & Medication

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.

Contents 1 Types of androgens 2 Androgen functions 2.1 Development of the male 2.2 Spermatogenesis 2.3 Inhibition of fat deposition 2.4 Muscle mass 2.5 Brain 3 Insensitivity to androgen in humans 4 References 5 See also

Types of androgens

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:

• 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.

• 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.

• Androstenediol: the steroid metabolite that is thought to act as the main regulator of gonadotropin secretion.

• 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.

• Dihydrotestosterone (DHT): a metabolite of testosterone that is actually a more potent androgen in that it binds more strongly to androgen receptors.

Androgen functions

Development of the male

During mammalian development, the gonads are at first capable of becoming either ovaries or testes[1]. 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[2]. 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^[3].

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^[4].

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^[5] and libido.

Insensitivity to androgen in humans

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.

References

1. ^ Online textbook: "Developmental Biology" 6th ed. By Scott F. Gilbert (2000) published by Sinauer Associates, Inc. of Sunderland (MA).
2. ^ Online textbook: "Endocrinology: An Integrated Approach" by S. S. Nussey and S. A. Whitehead (2001) published by BIOS Scientific Publishers, Ltd; Oxford, UK.
3. ^ 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) Entrez PubMed 16210377
4. ^ 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.
5. ^ 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) Entrez PubMed 16210377

See also

• antiandrogen