Somatomedin mediates:
Correct Answer: Deposition of chondroitin sulfate
Description: A i.e. Deposition of chondroitin sulfateGrowth hormone exes much of its effects (especially on growth, cailage & protein metabolism) through intermediate polypeptide growth factors also k/a somatomedin or insulin like growth factor secreted by liver & other tissues. The first of somatomedin isolated was called sulfation factor because it stimulated incorporation of sulfate into cailage (i.e. deposition of chondroitin sulfate)Q and collagen formation.SomatomedinsSomatomedins are polypeptide growth factors, secreted by liver and other tissues, which mediate the effects of growth hormone (somatotropin or STH) on growth, cailage and protein metabolism.Liver (and to a much lesser extent, other tissues) form somatomedins, when stimulated by somatotropin (or growth hormone). That is why gwoth hormone supplied directly to cailage chondrocytes cultured outside the body fails to produce proliferation & enlargement of chondrocytes whereas, growth hormone injections into intact living animal does cause it.Somatomedins are also k/a insulin like growth factors (IGFs) because many of its effects on growth are similar to effects of insulin on growth.At least 4 types have been isolated 3 of which are- Somatomedin A or insulin like growth factor 2 (IGF2) or multiplication stimulating activity (MSA) - Somatomedin B derived from vitronectin- Somatomedin C or IGF 1 is the most impoant type & its concentration closely follows the rate of growth hormone secretionThe principal & in humns probably the only circulating somatomedins are IGF1 & IGF-2. these factors closely relate to insulin, except that their C chains are not separated and they have an extension of A chain called the D domain. The activity that is not suppressed by antiinsulin antibodies is called non suppressible insulin like activity (NSILA). Most, if not all, of this activity persists after pancreatectomy and is d/t IGFland IGF II. However because of 100 fold weaker binding to insulin receptor the insulin like activity of IGF 1 & 2 is weak enough to prevent diabetes mellitus after pancreatectomy. Insulin also binds to IGF 1 receptors whereas IGFI & II bind to all 3 i.e. insulin, IGFI & IGF II receptorComparison of insulin & IGF InsulinIGF-IIGF-IIName-Somatomedin CMultiplicationstimulatingactivity (MSA)No. of aminoacids517067SourcePancreatic pcellsLiver, & othertissuesDiverse tissueLevelregulated byGlucoseGrowth hormoneafter bih,nutritional status?Plasma levels0.3-2 ng/mL10-700 ng/mLpeas at pubey300 -800 ng/mlPlasmabindingproteinsAbsentPresentPresentRoleMetabolismcontrolSkeletal &cailage growthGrowth duringfetal developmentSubstances with insulin like activity in plasma - Insulin- Proinsulin- Non suppressible insulin like activity (NSIL) d/t1. Low molecular weight fraction i.e. small amounts of free plasma IGF 1 and IGF2High molecular weight fraction i.e. large amounts of IGFs bound to proteins5 characteristic features of somatomedin Secretion is independent of growth hormone before bih but is stimulated by growth hormone after bih. Its concentration rises during childhood, peaks at pubey & then declines to low levels in old age.It has pronounced growth stimulating activity (epiphyseal growth & protein synthesis) Stimulates sulfate incorporation into cailage proteoglycan chondroitin sulfateQ- Insulin like effects on adipose tissue (antilipolytic) and muscles- Mitogenicity for fibroblasts- IGI- 1 receptor is similar to insulin receptor & uses same intra cellular signaling pathways.Characteristics of IGF- II- Hormone relaxin (both isoforms) resemble IGF-II- Largely independent of GH & plays a role in growth of fetus before bih.- If over expressed in fetus, growth of organs esp tongue other muscles, kidney, hea & liver is dispropoionate.- In adults IGF II gene is expressed only in choroids plexus & meninges- IGF II receptor has distinct structure & is involved in the intracellular targeting of acid hydrolyses & other proteins to intracellular organelles Pygmies of Africa & Levi-lorian dwarf have a - congenital inability to synthesize somatomedin C in adequate amount. Therefore, even though their plasma concentration of GH is either normal or high, they have diminished amounts of somatomedin C l/t small statures.IGF I & II are tightly bound to proteins (IGF binding protein 3 or IGFBP3 accounts for 95% binding) in plasma, at least for IGF I this prolongs their half life in circulation to about 20 hours. Whereas the growth hormone weakly binds to protein & has a sho half life of 20 minutes.It seems that GH & somatomedins can act both in cooperation & independently to stimulate pathways that 1/t growth. GH promote growth of muscle & bone. Its metabolic actions are counter regulatory to insulin as it induces glycogenolysis & gluconeogenesis in liver to increase blood glucose and mobilizes free fatty acids (i.e. lipolysis). It inhibits glucose uptake by muscle & fat cells, so more glucose is provided to brain & hea. Simultaneously, GH stimulates lipolysis in fat cells providing free fatty acids to hea & active skeletal muscle. But IGFI structurally similar to insulin is capable of increasing glucose utilization & decreasing lipolysis. These effects are opposite to those of acute, antiinsulin actions of GH.
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