RECOVERY OF GROWTH-HORMONE RELEASE FROM SUPPRESSION BY EXOGENOUS INSULIN-LIKE-GROWTH-FACTOR-I (IGF-I) - EVIDENCE FOR A SUPPRESSIVE ACTION OF FREE RATHER THAN BOUND IGF-I

To determine the time course of recovery of GH release from insulin-li ke growth factor I(IGF-I) suppression, 11 healthy adults (18-29 yr) re ceived, in randomized order, 4-h iv infusions of recombinant human IGF -I (rhIGF-I; 3 mu g/kg.h) or saline (control) from 25.5-29.5 h of a 47 .5-h fast. Serum GH was maximally suppressed within 2 h and remained s uppressed for 2 h after the rhIGF-I infusion; during this 4-h period, GH concentrations mere approximately 25% of control day levels [median (interquartile range), 1.2 (0.4-4.0) vs. 4.8 (2.8-7.9) mu g/L; P < 0. 05]. A rebound increase in GH concentrations occurred 5-7 h after the end of rhIGF-I infusion [7.6 (4.6-11.7) vs. 4.3 (2.5-6.0) mu g/L; P < 0.05]. Thereafter, serum GH concentrations were similar on both days. Total IGF-I concentrations peaked at the end of the rhIGF-I infusion ( 432 +/- 43 vs. 263 +/- 44 mu g/L; P < 0.0001) and remained elevated 18 h after the rhIGF-I infusion (360 +/- 36 vs. 202 +/- 23 mu g/L; P = 0 .001). Free IGF-I concentrations were approximately 140% above control day values at the end of the infusion (2.1 +/- 0.4 vs. 0.88 +/- 0.3 m u g/L; P = 0.001), but declined to baseline within 2 h after the infus ion. The close temporal association between the resolution of GH suppr ession and the fall of free IGF-I concentrations, and the lack of any association with total IGF-I concentrations suggest that unbound (free ), not protein-bound, IGF-I is the major IGF-I component responsible f or this suppression. The rebound increase in GH concentrations after t he end of rhIGF-I infusion is consistent with cessation of an inhibito ry effect of free IGF-I on GH release.