AR: androgen receptor
CYP: cytochrome P450
FSH: follicle-stimulating hormone
GnRH: gonadotropin-releasing hormone
hCG: human chorionic gonadotropin
LH: luteinizing hormone
NO: nitric oxide
PDE5: phosphodiesterase type 5
PKG: protein kinase G
sGC: soluble guanylate cyclase
TESTOSTERONE AND OTHER ANDROGENS
In men, testosterone is the principal secreted androgen. Leydig cells synthesize the majority of testosterone by the pathways shown in Figure 49–1. In women, testosterone also is the principal androgen and is synthesized 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.
Pathway of testosterone synthesis in Leydig cells of the testes. In Leydig cells, the 11 and 21 hydroxylases (present in adrenal cortex) are absent, but CYP17 (17α-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
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, the principal factor in male sexual differentiation, likely stimulated by human chorionic gonadotropin (hCG) secreted by the placenta. By the beginning of the second trimester, the serum testosterone concentration is close to that of midpuberty, about 250 ng/dL (Figure 49–2). Testosterone production then falls by the end of the second trimester, but by birth, the concentration is again about 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 about 250 ng/dL at 2 to 3 months after birth and falls to less than 50 ng/dL by 6 months, where it remains until puberty. During puberty, from about 12 to 17 years of age, the serum testosterone concentration in males increases so that by early adulthood the serum testosterone concentration is 300 to 800 ng/dL in men, compared to 30 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.
Schematic representation of the serum testosterone concentration from early gestation to old age.
Luteinizing hormone, secreted by the pituitary gonadotroph cells (see Chapter 46), is the principal stimulus of testosterone secretion in men, perhaps potentiated by follicle-stimulating hormone (FSH), also secreted by gonadotrophs. ...