1. Hypothalamic-Pituitary-gonadal axis
    • Hypothalamus releases gonadotropin-releasing hormone (GnRH)
    • GnRH controls the release of LH and FSH
    • LH and FSH cause release of androgens, estrogens and progesterone in the gonads
    • A,E and P cause negative feedback to stop release of GnRH, LH and FSH
  2. 3 Classes of anterior pituitary hormones
    • Somatotropic Hormones
    • Glycoprotein Hormones
    • POMC-derived Hormones
  3. Somatotropic hormones (3)
    • growth hormone
    • prolactin
    • placental lactogen
  4. Glycoprotein hormones (4)
    • Luteinizing hormone
    • Follicle-stimulating hormone
    • Human chorionic gonadotropin
    • Thyroid stimulating hormone
  5. POMC-derived hormones (2)
    • Corticotropin
    • alpha-Melanocyte stimulating hormone
  6. Posterior Pituitary Gland (3)
    • arginine
    • vasopressin
    • oxytocin
  7. Use of Estrogens and Progestins and agonists
    used for menopausal hormone therapy and contraception in women
  8. Use of Anti-Estrogens
    Treatment of hormone-responsive breast cancer and infertillity
  9. Most potent naturally occuring estrogen in humans
  10. Estrogen Phenolic A ring
    • Principle structural featur responsible for selective, high affinity binding to both receptors
    • Substitutions on the A Ring will impair binding.
  11. Estrogen C17
    Substitution of ethinyl group increases oral potency by inhiiting hepatic metabolism
  12. Diethylstilbestrol (DES)
    • binds with high affinity to both estrogen receptors
    • potent estradiol
    • much longer half-life
  13. Biosynthesis of steroidal estrogens
    • Androstenedione or testosterone aromatized by aromatase
    • Reaction is catalyzed by cytochrome P450 and uses NADPH and O2 as co-substrates
  14. Progesterone receptor
    • Favors ketone off ring at 3 position
    • double bond between 4 and 5
  15. Synthetic Progestins
    display limited binding to glucocorticoid, androgen and mineral corticoid receptors
  16. Non-specific progestins
    lack C19 methyl group
  17. Gonanes
    • Replace 13 methyl with 13 ethyl
    • Less androgenic activity
    • More potent progestin
    • Inactive dextrorotary isomer and active levorotatory isomer
  18. Cholesterol***
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  19. Synthesis of Testosterone
    Leydig cells of the testes synthesize testosterone from cholesterol
  20. Building block for cholesterol
    • acetate
    • plasma cholesterol
  21. Testosterone and its metabolites
    • Estradiol
    • Dihydrotestosterone

    Effects are mediated by testosterone itself or by other metabolites.
  22. Glucocorticoids
    • Potently suppress inflamation
    • Found in creams and ointments
  23. Hydrocortisone
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  24. coricosteroids
    No need for eninyl group at C17, --OH will work because it is topical and does not need to be metabolized in the liver
  25. Testosterone***
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  26. Estrogens***
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