The evolution of changes in immunoreactive serum insulin-like growth factors (IGFs), IGF-binding proteins, circulating growth hormone (GH) and GH-binding protein as a result of short-term dexamethasone treatment

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Abstract
Inhibition of growth in man and laboratory animals by glucocorticoid treatment is well recognized, yet we have previously shown that glucocorticoids may paradoxically enhance GH secretion and increase serum insulin-like growth factor (IGF) levels. IGFs circulate bound to high-affinity binding proteins (IGFBPs) which modulate their actions, and circulating GH may be associated with two binding proteins (GHBPs) of which the high-affinity GHBP has been characterized and is structurally identical to the extracellular domain of the GH receptor. We have investigated the time-course of changes in GH, IGFs and their binding proteins induced by glucocorticoid treatment in normal male volunteers (n=12, age range 22–31 years) sampled at 0800 h daily before and during treatment with dexamethasone (2 mg twice daily) for 5 days. In addition, subjects were sampled at 30-min intervals over 7-h periods (0730–1430 h) during the day prior to dexamethasone (day 0), on day 1 following the first dose of dexamethasone and on day 5 following the last dose of dexamethasone. Mean serum IGF-I rose over the initial 72 h and remained elevated at 96 h (297 ± 11·5 compared with basal levels of 215·5 ± 9·3 μg/l, PP=0·97). There was a concomitant rise in serum IGFBP-3 from basal levels of 3·69 ± 0·23 mg/l to a peak at 5 days of 4·16 ± 0·21 (P=0·003 vs day 1). Mean fasting IGFBP-1 levels fell significantly within 24 h, remaining low throughout the 5-day period whilst fasting insulin and C-peptide levels increased. IGFBP-2 rose within 24 h from basal levels of 315·5 ± 27·9 to 407·8 ± 27·3 μg/l at 24 h (P=0·01), then fell steadily to reach a nadir at 5 days of 240·4 ± 18·9 μg/l (P=0·02 vs basal levels). Peak GH secretion on day 1 (14·5 ± 3·7 μg/l) occurred between 4 and 5 h after dexamethasone administration. On day 5, the time of peak GH secretion was similar but the peak was attenuated (7·9 ± 1·2 μg/l, PP=0·001. The fall in GHBP as a result of dexamethasone treatment is in accordance with the reported inverse relationship between 24-h GH secretion and GHBP in health and disease states in man. This study has demonstrated clear temporal relationships between alterations in circulating levels of GH, IGF-I and IGFBP-1, -2 and -3 during dexamethasone treatment which support possible mechanisms whereby glucocorticoids induce a catabolic state through their endocrine and local tissue effects. Journal of Endocrinology (1994) 142, 547–554

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