somatotropic axis n.
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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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growth hormone
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
slide3
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
secretion pattern
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
slide5
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
regulation of gh secretion
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
slide8
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
effects of growth hormone
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
action of gh
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
slide12
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
slide13
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
slide15
Endocrine IGF-I
    • Potent inhibitor of GH synthesis and secretion
    • May not be essential for normal growth
slide19
Local IGF-I
    • Important for normal growth and development
    • Important for ovarian function
      • Steroidogenesis
        • Synergizes with gonadotropins
      • Cell proliferation