The androgens and oestrogens

The androgens and oestrogens represent the major male and female sex hormones respectively (Figure 11.B3). The testicular Leydig cells represent the primary source of androgens in the male, of which testosterone is the major one. Testosterone, in turn, serves as a precursor for two additional steroids, i.e. dihydrotestosterone and the oestrogen called oestradiol. These mediate many of its biological effects.

Females, too, produce androgens, principally in the follicular theca cells. Androgens are also produced in the adrenals in both male and females.

The biological activities of androgens (only some of which are specific to males) may be summarized as:

• promoting and regulating development of the male phenotype during embryonic development;

Testosterone

Testosterone

Oestrone

ß-Oestradiol Oestriol

Figure 11.B3 Androgen and oestrogen structures

• promoting sperm cell synthesis;

• promoting development and maintenance of male secondary sexual characteristics at/after puberty;

• general growth-promoting effects;

• behavioural effects (e.g. male aggressiveness, etc.);

• regulation of serum gonadotrophin levels.

The follicular granulosa cells are the major site of synthesis of female steroid sex hormones: the oestrogens. P-Oestradiol represents the principal female follicular oestrogen. Oestriol is produced by the placenta of pregnant females. Oestriol and oestrone are also produced in small quantities as products of P-oestradiol metabolism.

Testosterone represents the immediate precursor of the oestrogens, the conversion being catalysed by the aromatase complex, i.e. a microsomal enzyme system. The biological actions of oestrogens may be summarized as:

• growth and maturation of the female reproductive system;

• maintenance of reproductive capacity;

• development and maintenance of female secondary sexual characteristics;

• female behavioural effects;

• complex effects upon lipid metabolism and distribution of body fat;

• regulation of bone metabolism (oestrogen deficiency promotes bone decalcification, as seen in postmenopausal osteoporosis).

family of proteins. The inhibins are heterodimers consisting of a- and P-polypeptide subunits. Ac-tivins are PP dimers. The mature form of the a-subunit is termed ac, and it consists of 134 amino acid residues. Two closely related (but structurally distinct) P-subunit forms have been characterized: PA and PB. These exhibit in excess of 70 per cent amino acid homology and differ in size by only a single amino acid. The naming and polypeptide composition of the inhibin/activin family may be summarized as follows:

Inhibins and activins were initially identified as gonadal-derived proteins capable of inhibiting (inhibin) or stimulating (activin) pituitary FSH production (Figure 11.10). The major gonadal sites of inhibin synthesis are the Sertoli cells (male) and granulosa cells (female). In addition to

Female Male

- Positive feedback

Figure 11.10 Interrelationships between various hormones regulating reproductive function in the male and female. Particular emphasis is placed upon the regulatory effect many have on the production levels of additional reproductive hormones targeting the pituitary, the inhibins/activins likely play a direct (mutually antagonistic) role as paracrine/autocrine regulators of gonadal function.

They also likely induce responses in tissues other than the pituitary and gonads. In adults, for example, inhibin is also synthesized by the adrenal glands, spleen and nervous system. Recent studies involving inhibin-deficient transgenic mice reveal a novel role for inhibin as a gonadal-specific tumour suppressor. These mice, in which the a inhibin gene was missing, all developed normally, but all ultimately developed gonadal stromal tumours.

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