Growth hormone axis overview--somatomedin hypothesis.
The possibility that the action of growth hormone (GH) on cartilage is mediated by a separate hormonal agent found in serum was suggested by incubation with hypophysectomized rat costal cartilage. The stability of this tissue permitted long incubations and the measurement of the uptake of 35S-sulfate provided a convenient index of growth stimulation. Under the conditions arbitrarily selected, normal rat serum, but not serum from hypophysectomized rats, induced a great stimulation of 35S uptake. In contrast, GH added directly to cartilage in these incubations was virtually inactive. It was suggested that a serum sulfation factor, now known as insulin-like growth factor-I (IGF-I), was a mediator of GH action. Recently it has been observed that addition of 35S-sulfate after 24 h of preincubation with GH permitted the direct effect of GH to be recognized. Other observations in intact hypophysectomized rats have established that GH can induce the expression of IGF-I in cartilage that acts in an autocrine-paracrine manner. The relative importance of the endocrine and autocrine-paracrine routes of IGF-I action on the growth of cartilage is in dispute. It is clearly established that serum IGF-I exerts a negative feedback on GH secretion by action on the hypothalamus and pituitary. Serum IGF-I concentrations reflect GH action in postnatal life. Measurement of serum IGF-I is the most-valuable index of GH hypersecretion in acromegaly and in conditions of growth impairment. GH receptor deficiency leads to a marked decrease in circulating IGF-I. Hypernutrition and hyperinsulinism of obesity directly promote hepatic IGF-I release and inhibit GH secretion by the pituitary. Differences in hepatic IGF-I synthesis in response to GH may contribute to physiological differences in stature.
Department of Medicine, University of California, Irvine, USA.
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Daughaday
D000818:Animals; D002356:Cartilage / Q000254:growth & development; D004702:Endocrine Glands / Q000502:physiology; D006130:Growth Disorders / Q000097:blood; D013006:Growth Hormone / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000502:physiology; D008954:Models, Biological; D013002:Somatomedins / Q000502:physiology*
D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone