BIOSYNTHESIS OF TESTOSTERONE & STEROID HORMONES
The Leydig cells of the testis have the capacity to biosynthesize testosterone from cholesterol. Testosterone and its metabolically activated product dihydrotestosterone are critical for the development of male reproductive system and spermatogenesis. At least four steroidogenic enzymes are involved in testosterone biosynthesis.
The largest amounts of testosterone (>95%) are produced by the testes in men. It is also synthesized in far smaller quantities in women by the thecal cells of the ovaries, by the placenta, as well as by the zona reticularis of the adrenal cortex and even skin in both sexes. In the testes, testosterone is produced by the Leydig cells. The male generative glands also contain Sertoli cells, which require testosterone for spermatogenesis. Like most hormones, testosterone is supplied to target tissues in the blood where much of it is transported bound to a specific plasma protein, sex hormone-binding globulin (SHBG).
ANDROGEN SYNTHESIS IN MALES
Androgens are steroid hormones that control the expression and maintenance of male sexual characteristics
Adrenal androgens DHEA and androstenedione are produced in the zona reticulata and zona fasciculata of the adrenal cortex.
Testosterone is produced Leydig cells, which are found adjacent to the seminiferous tubules of the testes
In Leydig cells, LH initiates the production of pregnenolone
Pregnenolone is then converted to DHEA in a two-step process mediated by 17,20-lyase (17α-hydroxylase)
Because Leydig cells express high levels of 3β-HSD and 17β-HSD, DHEA is rapidly converted to testosterone via the intermediates androstenediol and androstenedione
Testosterone is converted to dihydrotestosterone (DHT) by the action of 5α-reductase in target tissues; although it is about one-tenth as abundant as testosterone, it accounts for most of testosterone’s biological action
ANDROGEN SYNTHESIS IN FEMALES
Although androgens are typically considered the male hormones, they also play important physiologic roles in females
Active androgens are largely created from circulating precursors in their target tissues, where they both act and are metabolized
Androgen precursors present in females include:
DHEA sulfate (DHEAS), produced by the zona reticularis of the adrenal glands;
DHEA, produced by the zona reticularis, ovarian theca cells, and peripherally from circulating DHEAS;
Androstenedione, produced by the zona fasiculata of the adrenal glands, the ovarian stroma, and peripherally from circulating DHEA
About 50% of testosterone in females is produced from circulating precursor molecules, with the other half synthesized in the zona reticularis and the ovarian stroma
DHT is also produced in females, but circulates in low concentrations in serum and is largely produced in peripheral target tissues
Testosterone, but not DHT, is converted to estradiol by the action of aromatase (P450aro) in certain peripheral tissues, and may be an important source of estrogens in postmenopausal women
In males, testosterone is synthesized primarily in Leydig cells. The number of Leydig cells in turn is regulated by luteinizing hormone (LH) and follicle-stimulating hormone (FSH). In addition, the amount of testosterone produced by existing Leydig cells is under the control of LH, which regulates the expression of 17-β hydroxysteroid dehydrogenase.
The amount of testosterone synthesized is regulated by the hypothalamic–pituitary–testicular axis (see figure to the right). When testosterone levels are low, gonadotropin-releasing hormone (GnRH) is released by the hypothalamus, which in turn stimulates the pituitary gland to release FSH and LH. These latter two hormones stimulate the testis to synthesize testosterone. Finally, increasing levels of testosterone through a negative feedback loop act on the hypothalamus and pituitary to inhibit the release of GnRH and FSH/LH, respectively.
The adrenal cortex is responsible for production of 3 major classes of steroid hormones: glucocorticoids, which regulate carbohydrate metabolism; mineralocorticoids, which regulate the body levels of sodium and potassium; and androgens, whose actions are similar to that of steroids produced by the male gonads.