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Growth Hormone

Growth Hormone. Victoria Brown. Structure of hormone. 191 amino acids long Protein structure 4 helices that help it bind its receptor 2 strong sulfide bonds hold the structure together. Structure of receptor. Single-chain glycoprotein receptor

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Growth Hormone

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  1. Growth Hormone Victoria Brown

  2. Structure of hormone • 191 amino acids long • Protein structure • 4 helices that help it bind its receptor • 2 strong sulfide bonds hold the structure together

  3. Structure of receptor • Single-chain glycoprotein receptor • 2 binding receptors for each molecule of growth hormone: • GHRI • GHRII • The 2 receptor molecules bind to two structurally distinct sites on opposite sides of a single growth hormone molecule • Binding of the two receptors is sequential, not simultaneous

  4. Where does it come from? • Synthesized and secreted by somatotroph cells (anterior pituitary) in response to growth-hormone releasing hormone (GHRH) from the hypothalamus • Activates gene transcription by cyclic adenosine monophosphate (cAMP) mechanisms

  5. What happens in the cell? • The hormone binds on the outside of the cell, bringing two receptors together • The interaction of growth hormone with its receptor leads to activation of cytoplasmic tyrosine kinases, triggering several enzymatic reactions and signaling processes that stimulate growth

  6. Role in growth • Growth hormone travels through the blood and stimulates the liver to produce a protein called insulin-like growth factor (IGF-1) • In children, IGF-1 stimulates chondrocytes to multiply in the cartilage at the ends of long bones (epiphyseal plate) • This leads to growth in the length of the bones and increases the child's height • In adults, growth hormone plays an important role inrepair and maintenance of the body’s tissues • IGF-1 also acts on immature muscle cells to increase muscle mass

  7. Role in metabolism • Protein metabolism: • Increased amino acid uptake • Increased protein synthesis • Fat metabolism: • Triglyceride breakdown in adipocytes (lipolysis) • Carbohydrate metabolism: • Helps maintain blood glucose levels • Suppresses insulin to prevent uptake of glucose in peripheral tissues • Glucose synthesis in the liver (gluconeogenesis)

  8. Primary Target tissues • Bone • Muscle • Fat

  9. Regulation • 2 hormones from the hypothalamus: • Growth hormone-releasing hormone (GHRH) • Stimulates both the synthesis and secretion of growth hormone • Somatostatin (SS) • Inhibits growth hormone release from somatotroph cells • 1 hormone from the stomach: • Ghrelin • Binds to receptors on somatotroph cells and potently stimulates secretion of growth hormone

  10. Negative Feedback • IGF-I • Directly suppresses the somatotroph cells • Stimulates the release of somatostatin from the hypothalamus • Growth hormone • Directly suppresses the somatotroph cells • Inhibits GHRH secretion

  11. Feedback

  12. Normal blood values • 1 - 9 ng/mL (male) • 1 - 16 ng/mL (female) • Natural levels of growth hormone fluctuate during the day, depending on: • Stress • Exercise • Nutrition • Sleep

  13. Too much growth hormone? • Usually from a tumor on the pituitary • Begins before puberty • Gigantism • Robert Wadlow • At birth: 8.5 lbs • 5 years old: 5’ 4” and 105 lbs • Adult: 8’ 11” and 490 lbs • Begins after puberty • Acromegaly • Enlarged face, hands, and feet • High blood pressure and heart disease • A number of metabolic derangements, including hyperglycemia

  14. Too little growth hormone? • Begins before puberty: • Dwarfism • Begins after puberty: • Reduction of muscle/bone strength and mass among other debilitating factors

  15. “There are no great limits to growth because there are no limits of human intelligence, imagination, and wonder.” —Ronald Reagan

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