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Human Endocrine Physiology

Human Endocrine Physiology. March 13, 2014. Binding Proteins. Hormone Binding Proteins. Usually produced by the liver Reversibly bind hormones Provide a pool of hormone in the circulation protected from metabolism Buffer changes in circulating free hormone levels:. T4 + TBG ↔ T4TBG. GnRH.

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Human Endocrine Physiology

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  1. Human Endocrine Physiology March 13, 2014

  2. Binding Proteins

  3. Hormone Binding Proteins • Usually produced by the liver • Reversibly bind hormones • Provide a pool of hormone in the circulation protected from metabolism • Buffer changes in circulating free hormone levels: T4 + TBG ↔ T4TBG

  4. GnRH 10 amino acid peptide hormone

  5. Male Reproductive Endocrinology Overview

  6. Testes Physiology GnRH - Pituitary LH FSH Testosterone - Testes Inhibin Sperm

  7. Puberty Adrenal activation Hypothalamic-pituitary-gonadal activation

  8. Adrenal Steroid Pathways ACTH Cholesterol Pregnenolone 17OH-Preg DHEA Progesterone 17OH-Prog Androstenedione Testosterone Cortisol Aldosterone

  9. Glycoprotein family of hormones

  10. Testes Steroid Pathways LH Cholesterol Pregnenolone 17OH-Preg Progesterone 17OH-Prog Androstenedione Testosterone

  11. Stages of puberty • Thelarche (breast development) • Adrenarche or pubarche (appearance of pubic/axillary hair) • Menarche

  12. Adrenal Steroid Pathways ACTH Cholesterol Pregnenolone 17OH-Preg DHEA Progesterone 17OH-Prog Androstenedione Testosterone Cortisol Aldosterone

  13. Adrenal Pathways:Pre-Adrenarche ACTH Cholesterol Pregnenolone 17OH-Preg DHEA Progesterone 17OH-Prog Androstenedione Testosterone Cortisol Aldosterone

  14. Adrenal Pathways:Post-Adrenarche ACTH Cholesterol Pregnenolone 17OH-Preg DHEA Progesterone 17OH-Prog Androstenedione Testosterone Cortisol Aldosterone

  15. Mechanisms of Activation of GnRH Secretion in Puberty

  16. Leptin • Peptide hormone produced by adipocytes • Multiple sites of action. • Reproductive axis. • More fat mass; more leptin • More leptin; more GnRH secretion (within normal limits of weight)

  17. Kisspeptin • Peptide hormone produced at various sites within the hypothalamus • Discovered in 1996 by cancer researchers at Penn State Hershey and named “metastin”. • In 2003, found to have a major role in controlling GnRH secretion; renamed “kisspeptin”. • Has receptors on GnRH neurons. • Stimulates GnRH secretion.

  18. Mechanisms of Activation of GnRH Secretion in Puberty • Increased GnRH secretion. • Via kisspeptin • Probable + effect of leptin on kisspeptin • Decreased sensitivity of the hypothalamus and pituitary to neg feedback from sex steroids.

  19. (animals) Granulosa Theca cells

  20. Increased kisspeptin stimulation of GnRH secretion (animals) Granulosa Theca cells

  21. Decreased sensitivity to negative feedback from sex steroids. (animals) Granulosa Theca cells

  22. Decreased sensitivity to negative feedback from sex steroids. (animals) Granulosa Theca cells

  23. Tanner Staging of Puberty

  24. Abnormal Puberty • Onset of secondary sexual characteristics • <8yo in girls • <9yo in boys • Delayed • Precocious

  25. Precocious Puberty • Gain of function mutation in the LH receptors • Defects in Kiss1 receptor

  26. Growth

  27. Growth Hormone

  28. Actions of GH • Protects against protein during calorie deprivation • Block proteolysis • Promotes use of fat as a source of energy to spare amino acids for protein synthesis • Promotes glucose genesis • Stimulates the liver to produce IGF-1 • Growth actions are generally mediated through IGF-1

  29. Factors StimulatingGH Secretion • Fasting or low glucose • Exercise • Sleep • Protein intake

  30. The Insulin-likeGrowth Factors • IFG-1: Responsible for anabolic actions of GH. • ↑ DNA, RNA and protein synthesis • ↑ Bone growth • IGF-2: Role is during fetal growth (later section)

  31. Similar structures of insulin and IGF-1 IGF-1

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