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DEMS: Unit III > Pituitary Physiology > Flashcards

Flashcards in Pituitary Physiology Deck (11):
1

Growth hormone - general notes on structure/function

  • Starts as prohormone
  • Contains many introns and exons, can be spliced for different types of GH
  • Most important type is 191 AA long
  • Signal peptide cleaved, stored in secretory granules of somatotrophs of adenohypophysis
  • Secretion controlled primarily by GHRH & somatostatin (GH feeds back on both of these)
    • GHRH --> increased GH --> increased cAMP
    • Somatostatin --> decreased GH --> decreased cAMP
  • Increased serum AA --> increased GH
    • Test by injecting arginine
  • Decreased serum glucose --> increased GH
    • Significant counter-regulatory hormone for insulin action
  • Metabolically GH dominates; with growth IGF dominates

2

Effects of GH malfunction (table)

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3

Prolactin: actions and MOA

  • Tonically inhibited by hypothalamic secretion of prolactin inhibitory hormone (PIH) aka dopamine
  • If hypothalamus is inhibited: adenohypophysis secretes larger amounts of PRL, other pituitary hormones
    • Lactotrophs secrete PRL
  • Principal target (and main site of action): breast (mammary gland)
    • Plays role in production of milk
  • High levels of PRL inhibit pulsatile secretion of GnRH by hypothalamic neurons
  • Specific receptors in: breast, liver, ovary, testis, prostate
  • Prolactin receptors --> members of growth hormone/cytokine receptor families
    • Long form of receptor: 620 AA's in length
    • Single chain proteins, cross the membrane only once
    • Ligand binding causes receptor dimerization --> activation of JAK/STAT pathway
  • PRL/GH share structural homology (so do their receptors)
  • PRL receptors well-stimulated by GH

4

Direct action of growth hormones on organs and systems

 

  • Adipose tissue
    • Increases lipolysis, leads to mobilization of lipids and increased FFAs in plasma
    • Leads to eventual loss of subcutaneous fat
    • GH is counter-regulatory to insulin
  • Muscle --> strong anabolic effect
    • Increases amino acid transport and protein synthesis
  • Liver --> increases RNA, protein, glucose synthesis
    • Increases IGF-1 secretion in presence of insulin, mediates indirect effects
    • Increases glucose due to increase in gluconeogenesis and glycogenolysis (small extent)
  • General --> GH is anti-insulin-like (decrease glucose uptake/increase glucose in plasma)
    • FFAs in plasma provide energy source
    • Glucose preserved for CNS
    • Protein sparing

5

Other effects of growth hormone on organs and systems

  • Fundamental for postnatal growth
    • Stimulates somatic growth
    • Regulates metabolism
  • Indirect actions: mediated via IGF-1
    • Powerful mitogen and growth-promoting agent

6

MOA of growth hormone through binding to its receptor

  • Cytokine receptor
  • Dimerizes on GH binding
  • Activates JAK/STAT pathway --> gene expression

7

Effects of IGF-1: bone/cartilage

  • Stimulates proliferation of epiphyseal plate
  • After puberty, linear growth at plate stops (growth plates close)

8

Effects of IGF-1: muscle

  • Stimulates proliferation, differentiation, protein synthesis 
  • Particularly post-puberty

9

Effects of IGF-1: adipose tissue

  • Stimulates uptake of glucose and inhibits lipolysis
  • Function is insulin-like and antagonizes GH

10

Effects of diet on IGF-1 function

  • Production of IGF-1 requires GH and insulin --> only grow in times of plenty!
    • Normal diet --> nice balance
    • Eating lots: increased serum AA --> increased GH and increased glucose --> increased insulin --> increased IGF
    • Starvation: decreased serum AA --> increased GH and decreased glucose --> decreased insulin --> no IGF
  • Thus in times of fasting: GH elevated but IGF-1 levels are depressed
    • Safety mechanism for body saying not to waste energy on growth

11

MOA of IGF-1

  • Receptors are EGF/Insulin receptor family
  • Inherent tyrosine kinase activity
  • Upon ligand binding, can readily phosphorylate themselves (autophosphorylation) and other proteins of signal transduction pathway
  • Major pathway --> IGF binds to insulin receptor associated proteins 1 and 2 (IRS I & II) --> IRS then bind other moelcules to activate either:
    • MAP kinase pathway, or
    • Transduction mediated by PI-3 kinase

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