AR: androgen receptor
AUC: area under the curve
cGMP: cyclic guanosine monophosphate
CYP: cytochrome P450
eNOS: endothelial nitric oxide synthase, NOS3
FSH: follicle-stimulating hormone
GnRH: gonadotropin-releasing hormone
hCG: human chorionic gonadotropin
HDL: high-density lipoprotein
LDL: low-density lipoprotein
LH: luteinizing hormone
NO: nitric oxide
PDE5: phosphodiesterase 5
PKG: protein kinase G
sGC: soluble guanylate cyclase
SHBG: sex hormone–binding globulin
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 45–1. 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 DHEA are weak androgens that can be converted peripherally to testosterone.
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 (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, probably stimulated by hCG from the placenta. By the beginning of the second trimester, the serum testosterone concentration is close to that of midpuberty, about 250 ng/dL (Figure 45–2). Testosterone production then falls by the end of the second trimester, but by birth the value is again about 250 ng/dL, possibly due to stimulation of the fetal Leydig cells by 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 2–3 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 ng/dL to 800 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.
Schematic representation of the serum testosterone concentration from early gestation to old age.