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

Inhibition of growth in man and laboratory animals by glucocorticoid t reatment is well recognized, yet we have previously shown that glucoco rticoids may paradoxically enhance GH secretion and increase serum ins ulin-like growth factor (IGF) levels. IGFs circulate bound to high-aff inity binding proteins (IGFBPs) which modulate their actions, and circ ulating GH may be associated with two binding proteins (GHBPs) of whic h the high-affinity GHBP has been characterized and is structurally id entical to the extracellular domain of the GH receptor. We have invest igated the time-course of changes in GH, IGFs and their binding protei ns induced by glucocorticoid treatment in normal male volunteers (n=12 , age range 22-31 years) sampled at 0800 h daily before and during tre atment 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 t he 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 remain ed elevated at 96 h (297 +/- 11.5 compared with basal levels of 215.5 +/- 9.3 mu g/l, P<0.001) whereas IGF-II levels did not change (472.6 /- 20.5 vs 450.3 +/- 21.7 mu g/l, P=0.97). There was a concomitant ris e in serum IGFBP-3 from basal levels of 3.69 +/- 0.23 mg/l to a peak a t 5 days of 4.16 +/- 0.21 (P=0.003 vs day 1). Mean fasting IGFBP-1 lev els fell significantly within 24h, remaining low throughout the 5-day period whilst fasting insulin and C-peptide levels increased. IGFBP-2 rose within 24h from basal levels of 315.5 +/- 27.9 to 407.8 +/- 27.3 mu g/l at 24 h (P=0.01), then fell steadily to reach a nadir at 5 days of 240.4 +/- 18.9 mu g/l (P=0.02 vs basal levels). Peak GH secretion on day 1 (14.5 +/- 3.7 mu g/l) occurred between 4 and 5 h after dexame thasone administration. On day 5, the time of peak GH secretion was si milar but the peak was attenuated (7.9 +/- 1.2 mu g/l, P<0.01 vs day 1 ). No morning rise in GH secretion had been observed prior to dexameth asone (day 0). GHBP fell steadily during the 5-day treatment period fr om basal levels of 29.3 +/- 1.9% to day 5 levels of 24.4 +/- 1.6%, P=0 .001. The fall in GHBP as a result of dexamethasone treatment is in ac cordance with the reported inverse relationship between 24-h GH secret ion and GHBP in health and disease states in man. This study has demon strated clear temporal relationships between alterations in circulatin g levels of GH, IGF-I and IGFBP-1, -2 and -3 during dexamethasone trea tment which support possible mechanisms whereby glucocorticoids induce a catabolic state through their endocrine and local tissue effects.