Hormone

  • hormone
    • substance synthesized in one organ & transport by circulatory system to act on other tissue
    • cholesterol derived
      • glucocorticoid
      • mineralocorticoid
      • estrogen
      • progestin
      • synthesized in final form & secrete immediately 
    • steroid 
      • progesterone - precursor of mineralocorticoid, glucocorticoid, androgen
    • polypeptide 
      • ACTH, TRH, PTH, GH
    • agonist - fool responder into thinking a hormone has bound 
    • antagonist - prevent bind 
  • Class
    • chemical composition
    • solubility properties
    • location of receptors
    • nature of signal produced 
    • G1 + ic receptor 
      • steroid hormone enter cell by simple diffusion
      • TH facilitated diffusion
      • androgen, calcitriol, estrogen, progestin, retinoic acid, glucocorticoid, mineralocorticoid, TH
      • lipophilic 
      • receptor in cytoplasm or nucleus 
    • G2 + cell surface receptor
      • 2nd mssger 
        • cAMp - a2 adrenergic catecholamine, b adrenergic catecholamine, ACTH, ADH, calcitonin, FSH, LH, TSH, glucagon, somatostatin
        • cGMP - atrial natriuretic factor, NO - potent vasodilator 
          • made from GTP by gaunylylcyclase
          • inhibitor: sildenafil (viagra) 
        • Ca/PI - acetylcholine, angiotensin, gastrin, TRH, oxytocin, ADH, PDGF
        • hormone epinephrine + receptor + G protein 7 span domain - Ga GDP +P to GTP, Gb & y separated 
        • activate adenylyl cyclase
        • ATP to cAMP
        • activate PK 
          • PKA heterotetramer 
          • 2 regulatory, 2 catalytic
          • 4cAMP + R2C2 = R2(4cAMP) + 2C
          • R2C2 not active catalytic
          • C active catalyze transfer of gamma phosphate of ATP to serine or threonine 
          • phosphatase -P 
          • phosphodiesterase convert cAMP to 5' AMP
          • caffeine - methylated xanthine, increase cAMP, prolong hormone action
        • activate protein 
      • G protein signaling disrupted
        • deficient or excessive G protein signal transmission
        • decrease G protein 
          • night blindness - mutation in Ga
          • pseudohypoparathyroidism - genetic loss of Ga
          • whooping cough
        • increase G protein
          • testotoxicosis - mutation in LH receptor - over produce testosterone
          • vibrio cholera - + ADP ribose to Ga - fatal diarrhea 
  • hormone receptor
    • 10^-18~-9 in ECF
    • recognition domain - + hormone ligand 
    • fx domain - generate signal 
    • protein
    • insulin receptor - heterotetramer a2 + insulin, b2 span membrane + tyrosine kinase activity 
  • steps
    • recognition of stimulus
    • hormone release
    • signal generation
      • autocrine signal - same cell
      • endocrine signal - neural, paracrine
      • synaptic signal - neuron, muscle
      • paracrine signal - c-c
    • effects 
      • G1 gene transcription
      • G2 gene transcription, channels transporters, protein translocation, protein modification
  • signal transduction
    • receptor + ligand
    • 2nd mssger - aa, peptide, FA, lipid
    • hydrophilic mssger + CM receptor
    • hydrophobic mssger + IC receptor

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