Androgens

Androgens

• Sources of androgens
  • males
    • testes are a major source of androgens
    • adrenal cortex is a minor source of androgens
  • females
    • adrenal cortex is a major source of androgens
• Androgen biosynthesis
  • adrenal cortex
    • in adrenal cortex, zona reticularis synthesizes and secretes adrenal androgens via a biosynthetic pathway that begins with cholesterol
      • androstenedione and dehydroepiandrosterone (DHEA)
  • testes
    • Leydig cells of testes synthesize and secrete testosterone via a biosynthetic pathway that begins with cholesterol
      • Leydig cells express 17β-hydroxysteroid dehydrogenase
        • catalyzes conversion of androstenedione to testosterone
      • Leydig cells lack 21β-hydroxylase and 11β-hydroxylase
        • testes cannot synthesize and secrete glucocorticoids and mineralocorticoids
    • Leydig cells of testis may also synthesize and secrete dihydrotestosterone (DHT)
      • Leydig cells express 5α-reductase
        • catalyzes conversion of testosterone to DHT
  • androgenic target tissues
    • in some androgenic target tissues, DHT is an active androgen
      • androgenic target tissues express 5α-reductase
        • catalyzes conversion of testosterone to DHT
• Androgen potency
  • DHT > testosterone > androstenedione
• Androgen function
  • actions mediated by testosterone 
    • fetal differentiation of internal male genitalia
      • epididymis, vas deferens, and seminal vesicles
    • pubertal growth spurt
      • growth of penis and seminal vesicles
      • deepening of voice
      • sex drive/libido in pre-pubescent males
    • increased muscle mass
    • cessation of pubertal growth spurt
      • epiphyseal plate closure
        • mediated by estrogen
          • testosterone → estrogen via aromatase
            • in testes, Sertoli cells express aromatase enzyme
              • catalyzes conversion of testosterone to estrogen
              • additionally, adipose tissue expresses aromatase enzyme
  • actions mediated by DHT
    • fetal differentiation of external male genitalia
      • penis, scrotum, and prostate
    • male hair pattern and male pattern baldness
    • sebaceous gland activity
    • growth of prostate
• 5α-reductase inhibitors 
  • e.g., finasteride
  • inhibit conversion of testosterone to DHT
  • DHT mediates male hair pattern and growth of prostate
    • 5α-reductase inhibitors may be used in treatment of benign prostatic hyperplasia (BPH) and hair loss in males
• Exogenous testosterone
  • exogenous testosterone inhibits hypothalamic-pituitary-gonadal axis
    • decreases testosterone levels in testes
      • decreases size of testes
      • causes azoospermia