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Glucocorticoids inhibit somatic growth in man and laboratory animals, and have long been regarded as suppressors of both stimulated GH secretion and insulin-like growth factor (IGF) activity. Recent evidence suggests, however, that glucocorticoids can be potent GH secretagogues in their own right with concomitant increases in circulating IGF-I levels. IGFs circulate tightly bound to a group of high-affinity binding proteins (IGFBPs) which modulate their actions. In order to investigate the effects of glucocorticoids on serum levels of IGFs and IGFBPs, normal male volunteers were sampled over 24-h periods before and directly after treatment with dexamethasone (2 mg twice daily) for 96 h. Following dexamethasone administration, all volunteers showed a marked increase in mean± S.E.M. IGF-I levels over the 24-h sampling period (292·2±31·8 before dexamethasone, 425·9 ±37 µg/l after dexamethasone, P<0·005); there was no change in mean IGF-II levels. Integrated mean insulin levels were raised by dexamethasone treatment (50 ±4·6 before dexamethasone, 117±13·4 mU/l after dexamethasone, P= 0·002) and IGFBP-1 was significantly suppressed (42·9±8·2) before dexamethasone, 28·0±7·9 µg/l after dexamethasone, P<0·001). IGFBP-2 levels were similarly suppressed after dexamethasone (319·5±24·5 before dexamethasone, 214·8±8·5 µg/l after dexamethasone, P=0·002), and there was a significant increase in IGFBP-3 levels from 3·24 ±0·25 to 3·67±0·32 mg/l (P=0·0153). Mean IGF bioactivity over the sampling period after dexamethasone was reduced by approximately 60% (0·93 ±0·39 before dexamethasone, 0·39 ±0·05 U/ml after dexamethasone, P <0·0001).
There were strong negative correlations between both insulin and IGF-I levels and those of IGFBP-2, suggesting the presence of a novel regulation mechanism for this binding protein. The established inverse relationship between insulin and IGFBP-1 was maintained after dexamethasone. These results suggest that glucocorticoids alter the bioactivity of IGFs, possibly by induction of inhibitors, but that neither IGFBP-1 nor IGFBP-2 can be implicated as glucocorticoiddependent inhibitors of IGF bioactivity in man. The study also demonstrates for the first time a strong negative correlation between IGF-I, insulin and IGFBP-2.
Journal of Endocrinology (1993) 136, 525–533
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