Reproductive Endocrinology

• Leydig cells


  Interstitial endocrinocytes found in the spaces between adjacent seminiferous tubules that secrete the male hormone testosterone
• Sertoli cells


  • Large cells embedded among the spermatogenic cells in the tubules
  • Form blood testes barrier
  • Nourish spermatocytes
  • Mediate the effects of testosterone and FSH on spermatogenesis
  • Phagocytose excess spermatids
  • Secrete the hormone inhibin which helps regulate sperm production by inhibiting production of FSH
• Hormones involved in control of spermatogenesis

  • GnRH (gonadotrophin-releasing hormone)
  • FSH (follicle stimulating hormone)
  • LH (luteinising hormone)
  • Testosterone
  • DHT (dihydrotestosterone)
  • Inhibin
• Hormone control of spermatogenesis

  1. At puberty GnRH secretion increases

  2. Stimulates anterior pituitary to secrete FSH and LH

  3. LH stimulates Leydig cells to produce testosterone

  4. Testosterone and FSH act on Sertoli cells to stimulate secretion of androgen-binding protein (ABP)

  5. Testosterone stimulates final stages of spermatogenesis

  6. When enough sperm have been produced Sertoli cells release inhibin which inhibits FSH
• Negative feedback system controlling testosterone production

  • Receptors in hypothalamus detect increased blood level of testosterone
  • Inhibits secretion of GnRH from hypothalamus
  • Reduced secretion of LH from anterior pituitary
  • Leydig cells secrete less testosterone
  • Blood level returns normal
• Causes of male hypogonadism

  • Primary congenital (inherited) - testicular agenesis, Klinefelter's syndrome
  • Primary acquired - bilateral orchitis, mumps, irradiation or cytotoxic drugs
  • Secondary (not testicular) - pituitary disorders, hypothalamic disorders
• Benign prostatic hyperplasia


  Enlargement of prostate, common in 1/3 of males over 60, causes frequent urination, decreased force of stream, bed-wetting & sensation of incomplete emptying
• Prostate cancer treatment


  • Blood test for prostate-specific antigen (PSA)
  • Antiandrogens such as flutamide or cyproterone are used to block testosterone/DHT actions and prevent them from stimulating prostate cancer cells to grow
• Erectile dysfunction treatment


  Viagra (Sildenafil citrate) - a PDE5 inhibitor that acts selectively in the arterial wall smooth muscle of the lungs and penis without inducing vasodilation in other areas of the body
• Phases of female reproductive cycle

  • Menstrual phase (days 1-5)
  • Pre-ovulatory phase (days 6-13)
  • Ovulation (day 14)
  • Postovulatory phase (days 15-28)
• Hormone control of female reproductive cycle

  1. GnRH secreted by hypothalamus controls ovarian and uterine cycle, stimulates release of FSH and LH from anterior pituitary

  2. FSH initiates follicular growth and stimulates ovarian follicles to secrete estrogens

  3. LH stimulates further development of ovarian follicles, triggers ovulation, promotes formation of corpus luteum

  4. Estrogens promote development and maintenance of female reproductive structures and secondary sex characteristics, inhibit release of GnRH, LH and FSH

  5. Progesterone works with estrogens to prepare and maintain endometrium for implantation and mammary glands for milk production, inhibits secretion of GnRH and LH

  6. Relaxin produced by corpus luteum relaxes uterus

  7. Inhibin secreted by growing follicles and corpus luteum inhibits secretion of FSH and LH
• Corpus luteum


  • If oocyte not fertilised, it degenerates in 2 weeks, ↓progesterone, estrogen and inhibin, ↑GnRH, FSH, and LH, allowing new ovarian cycle to begin
  • If oocyte fertilised, human chorionic gonadotropin (hCG) produced by chorion of embryo stimulates corpus luteum to continue secreting hormones
• Causes of female hypogonadism

  • Primary congenital (inherited) - Turner's syndrome, Noonan's syndrome
  • Primary acquired - chemotherapy, irradiation
  • Secondary - pituitary disorders, hypothalamus disorders
• Menopause


  • Hot flushes, copious sweating, headache, vaginal dryness, depression, weight gain, and emotional fluctuations
  • Short term treatment with HRT (oestrogen/progesterone) - Tibolone
  • Drawbacks of long term HRT therapy: ↑risk of endometrial cancer, ↑risk of breast cancer, ↑risk of venous thromboembolism
• Endometriosis treatment


  • GnRH analogues taken continuously to prevent oestrogen production
  • Progesterone without oestrogen (medroxyprogesterone acetate)
  • Danazol
• Breast cancer risk factors and treatments

  • BRCA1 and BRCA2 genes increase susceptibility
  • Treatments: hormone therapy, lumpectomy, mastectomy, radiation, chemotherapy, ovarian ablation, Tamoxifen, Herceptin, Anastrazole, Raloxifene
• Hormonal birth control methods

  • Combined pill (oestrogen/progesterone) - inhibits FSH and follicle development, inhibits LH preventing ovulation, makes endometrium unsuitable for implantation
  • Progesterone-only pill (levonorgestrel) - makes cervical mucus inhospitable for sperm, inhibits ovulation
  • Morning-after pill (emergency) - inhibits FSH and LH, induces menstruation
• Teratogens


  • Chemicals and drugs
  • Cigarette smoking
  • Irradiation
• Thalidomide


  Treat morning sickness, if taken in weeks 3-6 causes virtually 100% infant malformation - phocomelia (absence of development of limb bones)
• Hormone changes during pregnancy

  Cortisol is needed for maturation of lungs and production of surfactant
• Labor (parturition)


  1. Increase oestrogen softens cervix

  2. Increase relaxin from placenta dilates cervix

  3. Activation of stretch receptors in cervix

  4. Increase oxytocin release from posterior pituitary

  5. Syntocinon - oxytocin receptor agonist

  6. Contraction of uterine muscle pushes baby towards cervix
• Lactation (milk secretion & ejection)

  1. Oxytocin stimulates contraction of the myoepithelial cells in the breasts, which squeezes the glandular and duct cells and causes milk secretion

  2. Suckling stimulation ↑ oxytocin and ↓ PIH

  3. ↓ PIH results in ↑ secretion of prolactin, which maintains lactation