Chapter 41

### TESTOSTERONE AND OTHER ANDROGENS

In men, testosterone is the principal secreted androgen. The Leydig cells synthesize the majority of testosterone by the pathways shown in Figure 41–1. In women, testosterone also is probably the principal androgen and is synthesized both in the corpus luteum and the adrenal cortex by similar pathways. The testosterone precursors androstenedione and dehydroepiandrosterone are weak androgens that can be converted peripherally to testosterone.

###### Figure 41–1.

Pathway of synthesis of testosterone in the Leydig cells of the testes. In Leydig cells, the 11 and 21 hydroxylases (present in adrenal cortex) are absent but CYP17 (17 α-hydroxylase) is present. Thus androgens and estrogens are synthesized; corticosterone and cortisol are not formed. Bold arrows indicate favored pathways.

Secretion and Transport of Testosterone. The magnitude of testosterone secretion is greater in men than in women at almost all stages of life, a difference that explains many of the other differences between men and women. In the first trimester in utero, the fetal testes begin to secrete testosterone, which is the principal factor in male sexual differentiation, probably stimulated by human chorionic gonadotropin (hCG) from the placenta. By the beginning of the second trimester, the serum testosterone concentration is close to that of mid-puberty, ∼250 ng/dL (Figure 41–2) (Dawood and Saxena, 1977; Forest, 1975). Testosterone production then falls by the end of the second trimester, but by birth the value is again ∼250 ng/dL, possibly due to stimulation of the fetal Leydig cells by luteinizing hormone (LH) from the fetal pituitary gland. The testosterone value falls again in the first few days after birth, but it rises and peaks again at ∼250 ng/dL at 2-3 months after birth and falls to <50 ng/dL by 6 months, where it remains until puberty (Forest, 1975).

###### Figure 41–2.

Schematic representation of the serum testosterone concentration from early gestation to old age.

During puberty, from ∼12 to 17 years of age, the serum testosterone concentration in males increases to a much greater degree than in females, so that by early adulthood the serum testosterone concentration is 500 ng/dL to 700 ng/dL in men, compared to 30 ng/dL to 50 ng/dL in women. The magnitude of the testosterone concentration in the male is responsible for the pubertal changes that further differentiate men from women. As men age, their serum testosterone concentrations gradually decrease, which may contribute to other effects of aging in men.

LH, secreted by the pituitary gonadotropes (Chapter 38), is the principal stimulus of testosterone secretion in men, perhaps potentiated by follicle-stimulating hormone (FSH), also secreted by gonadotropes. The secretion of LH by gonadotropes is positively regulated by hypothalamic gonadotropin-releasing hormone (GnRH), and testosterone directly inhibits LH secretion in a negative feedback loop. LH is secreted in pulses, ...

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