13.10: Physiological Roles of Steroid Hormones

1. 13.10: Physiological Roles of Steroid Hormones Sierra Barnhart And Chelsalyn Corcoran

2. Synthesis of Steroid Hormones • Cholesterol is starting material for synthesis of Steroid Hormones. • Aliphatic side chain on the D ring is shortened. • Six Carbon unit is removed. • Secondary alcohol group on 3rd carbon is oxidized to a ketone. • Progesterone is produced. • Progesterone- starting compound for the sex hormones and adrenocorticoid hormones.

3. Adrenocorticoid Hormones • Products of the adrenal glands. • Classified in groups by function: • Mineralocorticoids-regulate concentration of ions. • Glucocorticoids- Control carbohydrate metabolism. • Corticoid- means site of secretion is the outer part of the gland. • Aldosterone- one of most important mineralocorticoids. Increased secretion enhances the re-absorption of Na+ and Cl- ions in kidney tubules. Increase the loss of K+

4. Continued…. • Na+ concentration controls water retention in tissues. Controls tissue swelling. • Cortisol- major glucocorticoid. Increase glucose and glycogen concentration. Fatty acids from body proteins are transported to liver, cortisol manufactures glucose and glycogen. Ketone derivative. Anti-inflammatory. Synthetic derivatives used for inflammatory diseases of organs: • Bronchial asthma, rheumatoid arthritis

5. Sex Hormones • Testosterone- most important male sex hormone • Promotes normal growth of genital organs • During puberty: testosterone production is increased • Causes deep voice, facial and body hair • Most important female sex hormone- estradiol • Synthesized from testosterone by aromatization of A ring.

6. Continued… • Estradiol and progesterone regulate menstrual cycle. • Beginning of cycle: estradiol rises causing the uterus lining to thicken. • The luteinizing hormone triggers ovulation. • If ovum is fertilized, progesterone will inhibit ovulation. Estradiol and progesterone prepare the uterine lining to receive the fertilized ovum.

7. Continued… • If no fertilization: progesterone stops and estradiol decreases. • Causes the uterine lining to thin down, and menstrual bleeding occurs • Blocking progesterone terminates a pregnancy • Progesterone interacts with a receptor in the nucleus of cells. • Receptor then changes its shape.

8. Mifepristone • Mifepristone also called RU486 acts as a competitor to progesterone. • Blocks the action of progesterone by binding to the same receptor cites. • Progesterone molecule can’t reach the receptor molecule so uterus isn’t prepared for implantation and ovum is aborted. • After pregnancy is established, RU486 will be taken up through 49 days of gestation.

9. Continued… • Supplement to surgical abortion. • Binds to the receptors of glucocorticoid hormones too • Used as an antiglucocorticoid. Also recommended to alleviate Cushing syndrome (overproduction of cortisone) • Morning after pill is different: • Can be taken up to 72 hours after unprotected intercourse • Acts before the pregnancy takes place

10. 2 kinds on the market as prescription drugs: • Levonogestrel- progesterone- like compound • Preven- combination of levonogestrel and ethynilestradiol • Estradiol and progesterone regulate secondary female sex characteristics. • RU486 used as an antiprogesterone can prevent certain types of breast cancer.

11. Male and Female Sex Hormones • Testosterone and estradiol are not exclusive to males or females. • A small amount of estradiol is produced in males • Small amount of testosterone in females • Only when hormonal balance becomes upset, can one have symptoms of abnormal sexual differentiation.

12. 13.11 What Are Bile Salts? • Oxidation products of cholesterol • Cholesterol is oxidized to the trihydroxy derivative • The end of the aliphatic chain is oxidized to the carboxylic acid. • The latter forms an amide bond with an amino acid.

13. Bile salts are powerful detergents • One end of the molecule is hydrophilic, due to its negative charge, and the rest is hydrophobic • Can spread dietary lipids in the small intestine into emulsions, facilitating digestion. • Similar to soap on dirt

14. Eliminated in feces • Remove extra cholesterol • Eliminated through bile salts • Solubilize deposited cholesterol in the form of cholesterol particles

15. 13.12 What are Prostaglandins, Thromboxanes, and Leukotrienes? • Prostaglandins • 1930s • KurzrokandLeib • Demonstrated semi fluid causes a hysterectomized uterus to contract • Ulf von Euler isolated the compounds from semen • Thought they came from prostate glad, thus prostaglandin

16. Seminal gland secretes 0.1 mg/ day in matured men • Small amounts present in both male and female • Synthesized from arachidonic acid by ring closure at carbons 8 and 12 • Cyclooxygenase (COX) catalyzes reaction • Product is PGG₂ • Persecutor of PGE PGF

17. E group has carbonyl group on carbon number 9 • Subscript represents number of double ponds in the hydrocarbon chain • F group – two hydroxyl groups on ring at 9 and 11

18. Cyclooxygenase • Two forms: • COX-1: catalyzes physiological production of prostaglandins (always present add more) • COX-2: responsible for prostaglandins in inflammation

19. Thromboxanes • Class of arachidonic acid derivatives is thromboxanes • Ring closure • Deived from PGH₂ • Ring is cyclic acetal • Induces platelet aggregation

20. Leukotrienes • Act to meditate hormonal responses • Derived from arachidonic acid • No ring closure

21. Occur mostly in white blood cells • Found in body tissue • Create long-lasting muscle contractions • Stronger than histamines

22. Cause fever and inflammation • Inhibiting uptake by leukotriene receptors stops effects • Zafirlukast helps to control chronic asthma