Steroid Hormones

1. Steroid Hormones Jenna Booth, Christa Beveridge, Abigail Ruths, and Paula Cook

2. 13.10 Physiological Roles of Steroid Hormones

3. Cholesterol is the starting material for the synthesis of steroid hormones • The alphatic side chain on the D ring is shortened with the removal of a six- carbon unit • Results in progesterone

4. Progesterone • Starting compound for • Sex hormones • Adrenocorticoid

5. Adrenocorticoid Hormones • Products of adrenal glands • Two groups • Mineralocorticoids • Regulate the concentrations of ions • Glucocorticoids • Control carbohydrate metabolism Corticoid-indicates that the site of the secretion is cortrex of the gland

6. Mineralocorticoids • Aldesterone is the most important • Increased secretion • Enhances the reabsorption • Increases loss of K • Controls tissue swelling

7. Glucorticoids • Cortisol is major glucocorticoids • Job is to increase the glucose and glycogen in the body • Fatty acid from fat storage cells and amino acids from body protiens to the liver • Antiinflamitory • Used to treat inflamatory diseases

8. Sex hormones • Male hormone-testosterone • Promotes normal growth of the male genital organ is synthesized in the testes from cholesterol Female sex hormones - most important is estradiol -regulates mensral cycle -level of estradiol increase when cycle begins

9. Continued… • LH (luteinizing Hormone)is another • Triggers ovulation • The ovulation increases progesterone level

10. Mifepristone blocks the action of progesterone • This is done by binding to the same receptor • Completely different approach is the morning pill • It has a progesertone-like compound called levonogestestrel

11. 13.11 Bile Salts

12. Products of cholesterol in oxidation • Cholesterol Trihydroxy derivative • End of aliphatic chain Carboxylic acid • Forms amide bond with amino acid (glycine or taurine) • Taurine has developed an importance in sports drinks • Ex) Red Bull contains sugars, caffeine and B vitamins as well as taurine

13. Bile salts are powerful detergents • One end is hydrophilic • Because of negative charge • The rest is hydrophobic • They can disperse dietary lipids in the small intestine into fine emulsions • Facilitates digestion • Similar to action of soap on dirt

14. Can also remove excess cholesterol in 2 ways • Breakdown cholesterol by themselves • Cholesterol is thus eliminated with bile salts • Solubilize deposited cholesterol in the form of bile salt- cholesterol particles

15. 13.12- Prostaglandins, Thromboxanes, & Leukotrienes

16. Prostaglandins • Prostaglandins: group of fatty-acid-like substances • Seminal gland secretes 0.1 mg of prostaglandin per day • Small amounts present throughout body of both sexes • Synthesized in body from arachidonicacid by a ring closure at carbons 8 & 12 • Enzyme catalyzing this reaction is cyclooxygenase (COX) • Product known as PGG2

17. Prostaglandins cont’d • Prostaglandin E group (PGE) has a carbonyl group at carbon 9 • Subscript indicates # of double bonds in hydrocarbon chain • Prostaglandin F group (PGF) has two hydroxyl groups on the ring at carbons 9 & 11 • Other prostaglandins (PGAs and PGBs) are derived from PGE • *diagram on page 294*

18. Prostaglandins cont’d • COX enzyme has 2 forms in body: COX-1 and COX-2 • COX-1: catalyzes normal physiological production of prostaglandins • Lowers blood pressure, treats asthma, decongestant • COX-2: responsible for production of prostaglandins in inflammation • Helps to produce new tissue in injuries such as: heart attack, rheumatic arthritis, & ulcerative colitis • *aspirin inhibits both COX enzymes*

19. Thromboxanes = another class of archidonic acid derivatives • Synthesis also includes a ring closure • Derived from PGH2, but ring is a cyclic acetal

20. Blood Clots • Thromboxane induces platelet aggregation • When blood vessel is ruptured, first line of defense is the platelets circulating in the blood. Forms an incipient clot • Thromboxane A2 causes other platelets to clump, increases clot

21. Blood Thinners • Aspirin and similar anti-inflammatory agents inhibit the COX enzyme • As a result, PGH2 and thromboxane synthesis is inhibited, and blood clotting is impaired • Many physicians recommend 81 mg aspirin a day for people at risk of heart attack or stroke • Forbid patients to use it before planned surgery  aspirin and other NSAIDs may cause excessive bleeding

22. PGH2 Thrombaxane A2

23. Variety of NSAIDs can inhibit COZ enzymes • Ibuprofin & indometacin (powerful painkillers) block aspirin’s effect • Eliminate anticlotting benefits • Use together is NOT recommended • Acetaminophen & diclophenac DON’T interfere, can be taken together

24. Leukotriens • Also act to mediate hormonal responses • Derived (like prostaglandins) from arachidonic acid by an oxidative mechanism • No ring closure

25. Leukotrienes occur mainly in white bloodcells • Also found in other body tissues • Produce long-lasting muscle contractions, especially in lungs • Can cause asthma-like attacks • Prostaglandins and leukotrines cause inflammation and fever

26. To counteract the effects of leukotrienes: • Inhibit their uptake by Leukotriene receptors (LTRs) in the body • Zafirlukast and Zileuton commercial drugs used to treat and control athsma