Effect of acute elevation of IGF-I on circulating GH, TSH, insulin, IGF-II and IGFBP-3 levels in non-endocrine short stature (NESS).

Abstract

It is not clear whether acute and slight elevation of serum IGF-I, which does not affect blood glucose levels, modulates circulating GH levels. To clarify this, small doses of recombinant human IGF-I (rhIGF-I, 5 microg/kg, i.v.) were administered as a bolus to 10 children with non-endocrine short stature (NESS) (5 males and 5 females, 11.2+/-0.7 yr old) after an overnight fast. Physiological saline was administered intravenously to sex- and age-matched NESS controls (5 males and 5 females, 10.9+/-0.7 yr old). The changes of serum GH, TSH, PRL, IGF-I, IGF-II, IGFBP-3, T4, T3 and plasma glucose levels after the administration were compared to those of the control subjects. Serum IGF-I levels increased significantly from 15 to 150 min after injection compared to those in the control group. The peak value was observed at 15 min (delta increment, 74.6+/-11.8 microg/l). At 15 min after the injection, serum insulin was suppressed significantly (p<0.05), although plasma glucose levels were not modified significantly. Serum TSH showed a significant decrease by rhIGF-I at 15 min and 60 min, whereas serum T4 and T3 levels were not modified. Serum GH was also significantly suppressed at 60 min (p<0.02) and showed a rebound increase at 120 min (p<0.05). Serum IGFBP-3 levels after rhIGF-I were higher than controls at 90 min and 150 min. No significant changes of serum PRL, IGF-II, (IGF-I plus IGF-II)/IGFBP-3 ratios were observed after the IGF-I injection compared to controls. These results indicate that circulating IGF-I is a physiological regulator of GH secretion in normal children, since the changes of IGF-I after the small doses of rhlGF-I administration were within physiological ranges and did not affect plasma glucose levels.