NEGATIVE FEEDBACK-REGULATION OF PULSATILE GROWTH-HORMONE SECRETION BY INSULIN-LIKE GROWTH-FACTOR-I - INVOLVEMENT OF HYPOTHALAMIC SOMATOSTATIN

To investigate the mechanisms of the negative feedback inhibition of growth hormone (GH) secretion by IGF-I, we studied parameters of GH pulsatility in six normal, fed men before and during a 48-h infusion of recombinant human IGF-I (rhIGF-I) (10-15 mu g/kg per h). Plasma levels of IGF-I increased from the baseline value of 163.5+/-9.3 mu g/liter (mean+/-SE) to a new steady state of 452.0+/-20.9 mu g/liter during the infusion. Plasma GH concentrations were measured every 10 min for 24 h during both saline and rhIGF-I infusions using a sensitive chemiluminescent assay. Overall, GH concentrations were suppressed during the rhIGF-I infusion by 85+/-3%, mainly by attenuating spontaneous GH pulse amplitude (77+/-4% suppression). The apparent GH pulse frequency was attenuated from 7.8+/-0.9 to 4.7+/-0.6 pulses/24 h (P = 0.006). Administration of rhIGF suppressed GH responses to exogenous GH-releasing hormone by 82+/-3%, and thyroid-stimulating hormone responses to thyrotropin-releasing hormone were also suppressed by 44+/-9%. This constellation of hormonal effects is most compatible with the rhIGF-I-induced stimulation of hypothalamic somatostatin secretion.