Steroid Hormones HO Cholesterol Starting material Steroid Sex Hormones • Androgens: male sex hormones • synthesized in the testes • responsible for the development of male secondary sex characteristics H3 C OH H3 C H3 C O H3 C HO Testosteron e And rosterone O Steroid Hormones • Among the synthetic anabolic steroids are: Prohormones, see p.515 H3 C CH3 OH H3 C H3 C H3 C O Chemical Connections 20G OH CH3 O Me th an di en on e Me th en ol on e Why are these hormones of interest? Do steroids really work? i.e. improve muscle mass and performance? . . . H3 C O H3 C O 4-An droste n e-3,17-di on e H3 C OH A resounding Yes . . . H3 C O H3 C HO Testosteron e And roste Steroid Sex Hormones • Estrogens: female sex hormones • synthesized in the ovaries from progesterone testosterone . . . (aromatization) estradiol • responsible for the development of female secondary sex characteristics and control of the menstrual cycle Steroid Sex Hormones A woman's monthly cycle w/o the pill (Blue and Red solid lines) A woman's monthly cycle on the pill (Blue and Red dashed lines) • Progesterone-like analogs are used in oral contraceptives: they Make the body think it is Pregnant at all times. . . preventing folicle stimulation and ovulation. . . •Steady stream of Progesterone required for implantation and development of oocyte Other pills block Progesterone all together. . .e.g. RU- 486 Progesterone Prevents egg from staying implanted . . Gets released. . . Steroid Hormones • Adrenocorticoid hormones • • • • synthesized in the adrenal cortex. regulate metabolism of carbohydrates. decrease inflammation. involved in the reaction to stress. Bile Salts • Bile salts, the oxidation products of cholesterol. • synthesized in the liver, stored in the gallbladder, and secreted into the intestine where they emulsify dietary fats and aid in their absorption and digestion H3 C HO CH3 H3 C HO CH3 NH COO- H3 C HO O OH Gl ycoch ol ate (from glycin e) H3 C HO OH Tau roch ol ate (from tau rin e) O NH SO 3 2 - Other Classes Lipids: - Prostaglandins - Thromboxanes - Leukotrienes • Prostaglandins: a family of compounds that have the 20-carbon skeleton of prostanoic acid. 9 5 7 1 3 8 6 4 2 12 14 16 18 COOH 10 11 13 15 17 20 19 Prostaglandins • Not stored in tissues - synthesized from membrane-bound 20-carbon polyunsaturated fatty acids in response to specific physiological triggers. • One such polyunsaturated fatty acid is arachidonic acid. 9 11 8 12 6 14 5 15 Arachid on ic acid COOH Prostaglandins 9 COOH 11 15 Arach i don i c aci d 2 O2 O O As pirin an d oth e r NS AIDs in h i bit thi s e n z ym e cycl ooxyge n as e (C O X) 9 COOH PGG 2 15 11 OOH O HO 9 9 COOH 11 HO COOH 15 OH PGE2 HO 11 15 OH PGF2 COX Enzymes • The COX (cyclooxygenase) enzyme occurs in two forms: • 1. COX-1 catalyzes the normal physiological production of prostaglandins. • 2. COX-2 is responsible for the production of prostaglandins in inflammation. • Tissue is injured or damaged, special inflammatory cells invade the injured tissue and interact with resident cells, e.g. smooth muscle cells or skin. • This interaction activates COX-2 and prostaglandins are synthesized. Aspirin helps relieve this anti-inflammatory response By inhibiting the production of prostaglandins . . . Thromboxanes • Thromboxanes are also derived from arachidonic acid. • Thromboxane A2 induces platelet aggregation and vasoconstriction. • Aspirin and other NSAIDs inhibit the synthesis of thromboxanes by inhibiting the COX enzyme. 9 10 11 8 1 COOH O O 12 15 OH Thromb oxan e A2 20 Challenge Questions How Does Aspirin prevent strokes caused by blood clots in the brain? NOTE: Doctors recommend 81mg/ day for people at risk for Heart Attack or stroke. . . Leukotrienes • Leukotrienes are also synthesized from arachidonic acid. • They occur mainly in leukocytes. • They produce muscle contractions, especially in the lungs and thereby can cause asthma-like attacks. • In this regard, they are 100 times more potent than histamine. • Several recently-developed anti-asthma drugs inhibit the synthesis of leukotrienes. OH OH 12 5 20 Leukotrien e B4 1 COOH