1 / 20

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

orestes-kristopher
Télécharger la présentation

Somatotropic axis

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  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

More Related