Growth Hormone

Growth Hormone

1. site of origin

   • Pituitary gland
     • anatomy
       • anterior lobe
         • paras anterior
           • acidophils
             • somatotropes
               • secrete GH
             • lactotropes
               • secrete prolactin
           • basophils
             • gonadotrophes
               • FSH and LH
             • cotricotrophes
               • ACTH
             • thyrotropes
               • TSH
           • chromophopes
         • paras intermediate
           • colloid filled cysts
             • secrete MSH
         • paras distalis
           • portal venules system
           • at medial eminence
       • posterior lobe
         • paras nervosa
           • infundibulum
             • medial emenince
       • infundiblum
         • connection with
           • hypothalamus

2. release of GH

   • physiology of hormone release
     • hypothalamic-hypophyseal tract
       • 1-hypothalamic nucleus secrete hormones
         • supraoptic--oxytocin
         • paraventricular -- ADH
           • 2-released into the axons
             • 3-stored in paras nervosa to be released when needed
     • hypophyseal portal system
       • 1-neuroendocrine cells in the hypothalamus secrete hormones
         • releasing hormones
         • inhibiting hormones
           • 2-released into the axons
             • 3-at he medial eminence, they get released into the portal venules to be carried to the anterior pituitary to stimulate or inhibit its hormonal releases
       • factors that regulate GH secretion
         • pattern of release: pulsatile

3. actions on the organs level

   • metabolic actions
     • CHO
       • hyperglycemic effect
         • muscles+adipocytes
           • -- glucose utilization
             • because of decreased sensitivity to insulin due to ++fatty acids level
               • GH
         • liver-++ gluconeogenesis
     • LIPID
       • increase lipid catabolism
         • adipocytyes
           • stimulate Hormone sensitive lipase to breakdown the fats
             • ++oxidation of fatty acids
         • liver
           • stimulate ketogenesis (because of excess acetyl Coa)
             • inhibit lipogenesis
     • PROTEIN
       • INCREASE protein anabolism
         • muscles
           • ++ aminoacids transport across membranes
           • ++ RNA translation into proteins by ribosomes
           • ++ DNA transcription into RNA to make proteins
           • DECREASE PROTEIN cataqbolism (protein sparing)
   • growth
     • go to liver and generate IGF-1
       • growth of bone
         • width
           • stimulate osteoblasts
             • increase bone desposition on the surface
               • increase in bone thickness
         • length
           • increase the metabolism of chondrocytes
             • increase the secretion of cartilage in the epiphyseal cartilage
               • increase the conversion of this cartilage into bone
   • actions in the cell-- 3 signal transduction pathways
     • JAK/STAT pathway
       • MAPK and PI3K/PKB pathways

4. pathologies and their treatment

   • GH excess
     • before epiphyseal closure
       • gigantism
         • increase in length to 8-9 feet
           • all tissue of the body growth rapidly
             • hypopituitarism
     • after epiphyseal closure
       • acromegaly
         • increase in bone thickness
           • growth in soft tissue (heart-kidney)
     • main cause: GH secreting tumor
     • treatment
       • main line is surgery-2nd line: radiation
         • 3rd line: pharmacological
           • Somatostatin analog
             • octreoline
           • Dopamine agonists
             • bromocreptine
           • GH receptor antagonists
             • pigvisomant
   • GH deficiency
     • main cause: hypopituitarism
     • child
       • pituitary dwarfism
         • patient becomes very short-sexual functions might be imparied
     • adult
       • generalized symptoms
         • decrease muscle mass - obesity -lack of energy - accelerated aging
     • treatment
       • depends on the cause
         • GH is deficient
           • recombinent hGH
             • Saizen
         • IGF-1 is deficient
           • rIGF-1
             • Mecasermin
         • Hypothalamic damage
           • Synthesitic GHRH
             • Sermorelin

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