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Somatotropic axis

Somatotropic axis. Growth hormone. Pituitary protein hormone 191 amino acids 22 kDa Non-glycosylated Two disulfide bridges Shares homology with prolactin, placental lactogen, and GH-variant Gene duplication. Human GH gene Located in chromosome 17 66 kb in length

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Somatotropic axis

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  1. Somatotropic axis

  2. Growth hormone • Pituitary protein hormone • 191 amino acids • 22 kDa • Non-glycosylated • Two disulfide bridges • Shares homology with prolactin, placental lactogen, and GH-variant • Gene duplication

  3. Human GH gene • Located in chromosome 17 • 66 kb in length • Cluster of genes that encode closely related genes • GH-V • Placental lactogen/chorionic somatotropins • Transcription of GH mRNA • POUF1 transcription factor • Pituitary specificity • Interacts with protein kinase A pathway

  4. Secretion pattern • Pulsatile manner • Interplay between GHRH and SS • Other GH secretagogues • Release of GH in response to GHRH • Elevation of cAMP • GHRH • Critical for development and maintenance of somatotrophs • Hypersecretion results in pituitary tumor development

  5. Role of SS • Affects timing and amplitude of pulsatile GH secretion • Pulsatile GH • Diminished secretion of SS coupled with increased GHRH secretion • Trough GH • Diminished secretion of GHRH coupled with increased SS secretion • Nature of GHRH/SS regulation of GH secretion • Somewhat unclear • Involvement of numerous neurotransmitters

  6. Regulation of GH secretion • Major GH pulses (70 % of total daily output) • Slow sleep (deep sleep) • Age-related loss of GH • Decrease quality of sleep • Obesity and diabetes • Decreased GH release • Nutritional status • One of the major regulatory factor of GH secretion

  7. Gender-specific pattern of GH secretion • Affects amount of steroidogenic enzymes • Gender-specific pattern of steroidogenesis • Gender-specific pattern of liver enzyme expression • Gender-specific action of GH • Mediated by STAT 5b activity

  8. Effects of growth hormone • Growth of epiphyseal plate in the long bones • Incorporation of sulfur into the epiphyseal cartilage • Sulfation factor • Indirect action of GH (delayed response) • Requirement of mediator(s) • Somatomedins

  9. Action of GH • Mediated by Insulin-like growth factors (IGFs) • Two types • IGF-I • IGF-II • Structurally similar to preinsulin • Interact with insulin receptor when in high concentrations

  10. IGF-II • Developmentally important • Declines with age • Secretion independent of GH in many species • IGF-I • Mediation of growth • Endocrine • Liver • Local (autocrine/paracrine) IGF-I • Secretion depends on GH

  11. Importance of IGF-I • Total deletion (knockout) • Postnatal lethality • 32-95 % die within 24 hr postpartum • Muscular dystrophy and premature lung development • Growth retardation • Embryonic • Postnatal (35 % less than that of normal) • Infertility • Impaired steroidogenesis

  12. Endocrine IGF-I • Potent inhibitor of GH synthesis and secretion • May not be essential for normal growth

  13. Local IGF-I • Important for normal growth and development • Important for ovarian function • Steroidogenesis • Synergizes with gonadotropins • Cell proliferation

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