[Somatomedins].
Somatomedins or insulin-like growth factors (IGFs) are two polypeptides (IGF I and IGF II) whose structure shows great homology with proinsulin. Mostly synthetized by the liver but also by many tissues, they circulate in blood bound to specific binding proteins (IGFBPs). IGFBP3, a 120 to 150 kDa complex, carries over 95% of blood IGFs and its production is stimulated by growth hormone (hGH). On the contrary, IGFBP1, a 40 to 50 kDa protein, increases in case of hGH-deficiency. An IGFBP of 34 kDa, which is the major BP in cerebrospinal fluid but also present in blood, shows a great affinity for IGF II whereas the others BPs show similar affinities for both IGFs. Little is known about the other BP, IGFBP2. Two receptors can be found in most tissues: type 1, which binds IGFs and insulin, type 2, which binds IGF II preferentially to IGF I but not insulin. Type 1 IGF receptor has structural and enzymatic (phosphorylation of one of its own sub-units) similarities with the insulin receptor and mediates the action of IGF I. Type 2 receptor has an homology with the bovine cation-dependent mannose-6-phosphate receptor and has no known function. Liver production of IGF I is mainly under the control of hGH and other factors such as diet; other tissues are less or not at all under the control of hGH. The blood levels of IGF I raise from birth to the end of puberty, then decrease and remain almost stable during adulthood. The activity of IGF I on skeletal growth is well established and the determination of its plasma levels by radioimmunoassay is of great clinical utility in the diagnosis of growth disorders. IGF I levels in blood are high in case of acromegaly, low in hGH-deficiency, undernutrition, hypothyroidy and renal failure. IGF I acts in an autocrine/paracrine way and probably endocrine sometimes. How IGF II synthesis is regulated is not well known, in any case, IGF II has no effect on growth and the regulation of its secretion is hardly influenced by hGH, its blood levels remain unchanged in acromegaly and are irregularly diminished in hGH-deficiency. Moreover, IGF I and II promote cellular growth and differentiation. This activity could be of great importance during fetal life.
Chevenne
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Hôpital Robert-Debré, Service de Biochimie-Hormonologie, Paris.
D000818:Animals; D001681:Biological Assay / Q000379:methods; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D011956:Receptors, Cell Surface / Q000302:isolation & purification; D013002:Somatomedins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism
D002352:Carrier Proteins; D011956:Receptors, Cell Surface; D013002:Somatomedins
Les somatomédines.