Describe the actions and regulation of testosterone. Add a note on puberty in the male.

Source and Nature

• Secretion 4–9 mg/day; plasma level 300–1000 ng/dL
• Small amounts from the adrenal cortex and, in women, the ovary
• Transported bound to sex hormone binding globulin (60%) and albumin; only 2% is free and active

Active Metabolites

• DHT is 2–3 times more potent than testosterone
• Finasteride inhibits 5α-reductase — used in benign prostatic hyperplasia and male-pattern baldness

Actions

A. Before birth

• Differentiation of the Wolffian duct → epididymis, vas deferens, seminal vesicle
• DHT → development of the external genitalia and prostate
• Descent of the testes in the last trimester
• Anti-Müllerian hormone from Sertoli cells causes regression of the Müllerian duct

B. At puberty and after

Regulation

Hypothalamus → GnRH (pulsatile, every 90 min) → Anterior pituitary → LH → Leydig cell → testosterone → Negative feedback on hypothalamus and pituitary

• Pulsatile GnRH is essential — continuous GnRH down-regulates its receptors and suppresses the axis. This is exploited by GnRH agonists in prostate cancer
• Diurnal variation — highest in the early morning; samples must be taken then

Puberty in the Male

• Begins at 9–14 years; the first sign is testicular enlargement (> 4 mL)
• Trigger — reactivation of pulsatile GnRH, with leptin from adipose tissue acting as a permissive signal of adequate nutrition
• Sequence — testicular growth → pubic hair → penile growth → growth spurt → voice change → facial hair
• Growth spurt occurs late in boys but early in girls — which is why girls are temporarily taller

Accessory Sex Glands

• All three are androgen dependent — they atrophy after castration
• PSA is the tumour marker for prostatic carcinoma; it also rises in benign hyperplasia and prostatitis

Applied Aspects

• Klinefelter syndrome (47, XXY) — small firm testes, gynaecomastia, tall eunuchoid build, azoospermia; ↑ FSH and LH with low testosterone
• Androgen insensitivity syndrome — 46 XY with defective receptors → female external genitalia, absent uterus, testes intra-abdominal
• 5α-reductase deficiency — ambiguous genitalia at birth that virilise at puberty
• Anabolic steroid abuse → testicular atrophy and infertility, through feedback suppression of LH and FSH
• Benign prostatic hyperplasia — DHT dependent; treated with finasteride and α-blockers
• Male hypogonadism — primary (testicular; FSH and LH high) or secondary (pituitary or hypothalamic; FSH and LH low). The gonadotrophins distinguish them
• Erectile function — erection is parasympathetic (nitric oxide, "point"), ejaculation is sympathetic ("shoot")
• Sildenafil inhibits phosphodiesterase-5 → ↑ cGMP → cavernosal smooth muscle relaxation
• Gynaecomastia — from a raised oestrogen : androgen ratio; seen in puberty, cirrhosis, Klinefelter syndrome and with spironolactone or digitalis
• Andropause — testosterone falls gradually from about 40 years, unlike the abrupt menopause
• Testicular torsion — a surgical emergency; the testis is irreversibly damaged after about 6 hours of ischaemia