7. Repro Endocrinology 2010

7. Repro Endocrinology 2010 - Reproductive Endocrinology...

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Unformatted text preview: Reproductive Endocrinology Reproductive Endocrinology • Hypothalamic hormones – Gonadotropin releasing hormone (GnRH) - stimulate release of • FSH = follicle stimulating hormone • LH = luteinizing hormone – from pituitary • ‘Gonadotropin’ = gonad stimulating Hypothalamic Surge/Tonic Centers • Neurosecretory neurons from surge and tonic centers deposit neurohormones into portal system • Portal system delivers these hormones to the adenohypophysis GnRH release is pulsatile • GnRH pulse generator in hypothalamus called ‘circhoral clock’ • Circhoral pulses • One pulse every hour • Each LH peak coincides with a GnRH pulse Adenohypophysis Adenohypophysis Pituitary Glycoproteins FSH - LH - TSH Pituitary Hormones • Follicle stimulating hormone – stimulates gametogenesis in males and females • Luteinizing Hormone – stimulates steroidogenesis in males and females • Prolactin – stimulates the synthesis of milk in mammalian females – maternal behavior in some species • Oxytocin – stimulates smooth muscle contraction • associated with birth and milk release Negative Feedback Hypothalamus Pituitary GnRH FSH/LH Short Feedback Gonad Gonad Negative Feedback Hypothalamus Pituitary GnRH Long Feedback LH T or E Gonad Gonad Negative Feedback & Homeostasis Hormone Conc Hormone Conc T or E Time GnRH GnRH LH Negative feedback Negative • 1. peptide hormones • alter G protein response • E2 and P4 decrease transcription of ßFSHßFSHmRNA and levels of ßFSH-mRNA mRNA ßFSH-mRNA • P4 causes decrease in GnRH release release • 2. steroid hormones Positive Feedback & Homeostasis Hormone Conc Hormone Conc E Time GnRH GnRH LH Permissive action of hormones Permissive • steroid hormones may act as permissive agents by • increase number of receptors • increase protein kinases increase kinases • increase inhibitors of cyclic nucleotides Other Endocrine Organs Other • gonads • steroids • synthesis stimulated by LH • derived from cholesterol Steroidogenesis C holesterol P450ssc 3!HSD Pregnenolone Isomerases Progesterone P450c21 Deoxycorticosterone P450c11 Corticosterone P450c17 3!HSD 17-OH Pregnenolone Isomerases P450c17 P450c21 17-OH Progesterone 11 Deoxycortisol P450c11 Cortisol P450c17 3!HSD P450c17 Testosterone P450 arom 17! Estradiol 17 Keto Dehydroepiandrosterone Androstenedione Reductase Isomerases Progestagens Progestagens • Primary progestagen Primary progestagen • Secondary progestagens Secondary progestagens • Progesterone • 17α-Hydroxyprogesterone (17α-OHP) • 20α-Hydroxyprogesterone (20α-OHP) Hydroxyprogesterone (20 • Aka 20α-dihydroxyprogesterone Aka 20 • Three nuclear receptors • Membrane receptors (two distinct classes) • progesterone membrane receptor component • (PGMRC; subtypes 1 and 2) • PR-A; PR-B and new PR-C (humans to date) • membrane progestin receptors • (mPR; subtypes alpha, beta and gamma) Androgens • Androgens • two 1° androgens • Testosterone (T) • dehydrotestosterone (DHT) dehydrotestosterone (DHT) • Androstenedione (A4) Androstenedione (A4) • Dehydroepiandrosterone (DHEA) Dehydroepiandrosterone (DHEA) • AR • two 2° androgens • One nuclear receptor • One membrane receptor? • Characterization/no cloning and sequence to date Estrogens Estrogens • in vertebrates • • • • • • three 1° estrogens (Oestrogens) Estradiol-17β (E2) Estriol Estrone ERα ERβ • Two nuclear receptors nuclear • One membrane receptor • GPR30 GABAR GIRK K+ PKC E2 PLC G mER Src Ras SOS GRB2 Shc RTK mER E2 Raf MEK MAPK PI3K Ca 2+ µ AC 2+ cAMP PKA Ca Akt eNOS NO p p CREB AP1 Non-ERE-promoter CyclinD1 E2 CyclinD1 p FoxA1 coactivator nER p E2 p coactivator nER p ERE-promoter ERE-promoter FoxA1 Cholesterol Gain carbonyl groups Loss carbon tail Progesterone Testosterone Gain hydroxyl Loss carbonyl & methyl Estradiol-17β Adrenal Adrenal • Mineralocorticoids • Glucocorticoids • aldosterone • cortisol or corticosterone cortisol corticosterone • Dehydroepiandrosterone (DHEA) Dehydroepiandrosterone (DHEA) • Weak Androgens • All derived from progesterone Adrenal Adrenal • Mineralocorticoids • aldosterone • Glucocorticoids • cortisol or corticosterone cortisol corticosterone • Weak Androgens • Dehydroepiandrosterone (DHEA) Dehydroepiandrosterone (DHEA) • All derived from progesterone • Major role in stress response Adrenal Function Steroidogenesis Lipid based Hormones Prostaglandins • Eicosanoids • Along with thromboxanes and prostacyclins • Lipid based hormones • 20 carbon atoms, • 5-carbon ring • Derived from arachidonic acid Prostaglandins • First isolated from seminal fluid in 1935 • by the Swedish physiologist Ulf von Euler • and independently by M.W. Goldblatt • believed to be from prostate • Actually produced by the seminal vesicles • Produced in virtually all tissues and organs • autocrine and paracrine mediators • act upon multiple cell types • platelets, endothelium, uterine and mast cells • Non-Steroidal Anti-Inflammatory Drug (NSAID) • Target COX and other aspects of PGs pathways Prostaglandins Prostaglandin blockers - NSAIDs Unintended Consequences • FDA • more than 22,000 dogs have gotten sick • some have died after taking non-steroidal anti-inflammatory drugs • including Metacam, Deramaxx, Previcox and Rimadyl. http://www.dogsadversereactions.com/nsaid/nsaidspage.html Diclofenac (NSAID) and Vultures • Unintended consequences • Not all species the same • Diclofenac • Non-Steroidal Anti-Inflammatory Drug (NSAID) • cause gout and renal failure in vultures of the Gyps genus • In India 3 Gyps species • lost over 99 percent of population in a decade • Still sold in Africa • Used for cattle http://envfor.nic.in/divisions/wildlife/vulture_plan.htm Thyroid Thyroid • thyroxin (T4) or triiodothyronine (T3) triiodothyronine (T • iodine as a central component • alters metabolism • nuclear receptor in mitochondria Thyroid • Two lobes in the neck • Two hormones • Major role in development and control of metabolism • Thyroxine (T4) • Triiodothyronine (T3) • Require iodide for synthesis Thyroid follicle ...
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This note was uploaded on 05/19/2011 for the course ZOO 4926 taught by Professor Staff during the Summer '08 term at University of Florida.

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