Androgens (from Greek ἀνήρ, ἀνδρός anér, andrós "man"; -gen "generating" from γίγνομαι gígnomai "become") are sex hormones that have a virilizing effect (from Latin virilis "male") and thus the development of secondary sexual characteristics such as beard growth , Muscle development and deepening voices in adolescents. Androgens are produced in the testes and adrenal glands and, to a lesser extent, in the ovaries .
Its backbone is the androstane (10 β , 13 β -dimethyl gonane ). Androgen is the generic term for any natural or synthetic substance, usually a steroid hormone , that stimulates or controls the development and maintenance of male characteristics in vertebrates by binding to androgen receptors . This includes the activity of the accessory male genital organs and the development of male secondary sexual characteristics . Androgens, which were first discovered in 1936, are also known as androgenic hormones or testoids . Androgens are also the original anabolic steroids . They are also the precursors of all estrogens , the female sex hormones. The main androgen best known before androsterone is testosterone .
A subgroup of androgens, adrenal androgens , includes all 19-carbon steroids that are formed by the adrenal cortex ; H. from the outer portion of the adrenal gland , and which act as weak steroids or steroid precursors, and the like. a. Dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA-S) and androstenedione.
In addition to testosterone , other androgens include:
- Dehydroepiandrosterone (DHEA): a steroid hormone made from cholesterol in the adrenal cortex, which is the main precursor of natural estrogens. DHEA is also known as dehydroisoandrosterone or dehydroandrosterone.
- Androstenedione ("Andro"): an androgenic steroid made by the testes, adrenal cortex, and ovaries. Androstenediones are metabolically converted to testosterone and other androgens, but they are also the starting structure of estrone . The use of androstenedione as a dietary supplement to improve performance in athletes or in bodybuilding has been banned by the International Olympic Committee and other sports organizations.
- Androstenediol : a steroid metabolite believed to act as the main regulator of gonadotropin secretion .
- Androsterone : a chemical by-product that arises from the breakdown of androgens or comes from progesterone , and also has slight masculinizing effects, but only at one-seventh the intensity of testosterone. It is found in roughly equal amounts in the plasma and urine of men and women.
- Dihydrotestosterone (DHT): a metabolite of testosterone; is actually a more potent androgen in that it binds more strongly to androgen receptors.
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- in men : Leydig cells of the testicle , adrenal cortex
- in women : ovaries and adrenal cortex
Development of man
During the development of mammals, the sex glands (gonads) are initially able to develop into both the ovary and the testicle . In humans, from about the fourth week onwards, the anlage of the sex glands is present in the intermediate mesoderm near the developing kidneys. Around week 6, epithelial genital cords form within the developing testes and take up the gametes (germ cells) as they migrate into the sex glands. In men, certain Y chromosome genes, particularly SRY, control the development of the male phenotype, including the conversion of the early bipotential sex gland into the testes. In men, the genital cords completely penetrate the developing sex glands.
By week 8 of human fetal development, Leydig cells appear in the male's differentiating sex glands. The epithelial cells of the genital cords originating from the mesoderm in the developing testes develop into the Sertoli cells, which have the function of supporting the formation of sperm cells. A smaller population of non-epithelial cells is found between the seminiferous tubules; these cells are the androgen-producing Leydig cells. The Leydig cells can be thought of as the producers of androgens, which act as paracrine hormones needed by the Sertoli cells to support sperm production. Soon after they differentiate, Leydig cells begin to produce androgens, which are necessary for the masculinization of the developing male fetus (including the formation of the penis and scrotum). Under the influence of androgens, remnants of the mesonephrosis , the Wolff's ducts , the epididymis , the vas deferens duct and the seminal vesicles develop . This effect of the androgens is supported by a hormone from the Sertoli cells AMH , which prevents the development of the embryonic Müller ducts into fallopian tubes and other tissues of the female reproductive system in male embryos. AMH and androgens work together to allow the testicles to migrate normally into the scrotum.
Before the formation of the pituitary hormone LH by the embryo, which begins around the eleventh to twelfth week, human chorionic gonadotropin ( hCG ) promotes the differentiation of Leydig cells and their formation of androgens. The androgen action in the target tissues often involves a conversion of testosterone to 5α-dihydrotestosterone ( DHT ).
During puberty, the production of androgens, LH and FSH increases , the genital cords hollow out and the testicular tubules form, and the germ cells begin to differentiate into sperm. Throughout adulthood, androgens and FSH work together on the Sertoli cells in the testes to help produce sperm. Exogenous androgen supplements can be used as a pill for men . Elevated androgen levels caused by the use of androgen supplements can inhibit the production of LH and block the production of endogenous androgens by Leydig cells. Without the locally high concentrations of androgens in the testes due to androgen production by the Leydig cells, the seminiferous tubules can degenerate, leading to infertility.
The prostate is one of the androgen-dependent organs. Androgens are essential for the survival of the prostate gland cell. Androgens also play an important role in the development of prostate carcinoma . Withdrawal from androgens ( androgen deprivatation ) is an important treatment modality for prostate cancer. Androgen receptor content and receptor mutations in prostate tumor cells influence the effectiveness of androgen deprivatation. If a prostate carcinoma continues to grow despite androgen deprivation, it is called a castration-resistant tumor ( HRPC , hormone resistant prostate carcinoma).
Inhibition of fat deposition
Men typically have less fat tissue than women. Recent results indicate that androgens inhibit the ability of certain fat cells to store lipids (fats). Physiologically, this takes place via the inhibition of a signal transduction pathway that normally supports the function of fat cells ( adipocytes ).
Men typically have more skeletal muscle mass than women. Androgens promote the enlargement of skeletal muscle cells and are likely to have a coordinated effect to improve muscle function by influencing various cell types in skeletal muscle tissue.
Circulating levels of androgens can affect human behavior because certain nerve cells are sensitive to steroid hormones. The androgen levels are said to be involved in the regulation of human aggression .
Androgen insensitivity in humans
The reduced ability of a fetus with XY - karyotype to respond to androgens can result in one of several problems, including infertility and several forms of intersex conditions .
- ^ Scott F. Gilbert: Developmental Biology . 6th ed. Sinauer Associates, Sunderland MA 2000.
- ↑ S. S. Nussey, S. A. Whitehead: Endocrinology: An Integrated Approach . BIOS Scientific Publishers, Oxford UK 2001.
- ↑ Jose D Debes, Donald J Tindall .: Mechanisms of Androgen-Refractory Prostate Cancer. In: The New England Journal of Medicine . tape 351 , no. 15 , 2004, pp. 1488-1490 .
- ↑ R. Singh et al .: Testosterone inhibits adipogenic differentiation in 3T3-L1 cells: nuclear translocation of androgen receptor complex with beta-catenin and T-cell factor 4 may bypass canonical Wnt signaling to down-regulate adipogenic transcription factors. In: Endocrinology. Vol. 147 (2006), pp. 141-154. PMID 16210377 doi: 10.1210 / en.2004-1649 .
- ↑ I. Sinha-Hikim et al .: Androgen receptor in human skeletal muscle and cultured muscle satellite cells: up-regulation by androgen treatment. In: J. Clin. Endocrinol. Metab. Vol. 89 (2004), pp. 5245-5255. PMID 15472231 . doi : 10.1210 / jc.2004-0084 .
- ↑ M. Giammanco et al .: Testosterone and aggressiveness. In: Med. Sci. Monit. Vol. 11 (2005), pp. RA136-RA145. PMID 15795710 PDF .