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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-I¹

Division of Endocrinology and Metabolism, Department of Medicine (I.M.C., M.L.H., E.H.S., S.S.P., M.O.T.), and Division of Biostatistics and Epidemiology, Department of Health Evaluation Sciences (K.S.P.), University of Virginia Health Sciences Center, Charlottesville, Virginia 22908; and the Department of Pediatrics, Stanford University Medical Center (R.L.H.), Stanford, California 94305

Address all correspondence and requests for reprints to: Dr. Michael O. Thorner, Department of Medicine, Box 466, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908.

To determine the time course of recovery of GH release from insulin-like growth factor I (IGF-I) suppression, 11 healthy adults (18–29 yr) received, in randomized order, 4-h iv infusions of recombinant human IGF-I (rhIGF-I; 3 µg/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 suppressed for 2 h after the rhIGF-I infusion; during this 4-h period, GH concentrations were approximately 25% of control day levels [median (interquartile range), 1.2 (0.4–4.0) vs. 4.8 (2.8–7.9) µg/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) µg/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 µg/L; P < 0.0001) and remained elevated 18 h after the rhIGF-I infusion (360 ± 36 vs. 202 ± 23 µg/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 µg/L; P = 0.001), but declined to baseline within 2 h after the infusion. The close temporal association between the resolution of GH suppression 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 for this suppression. The rebound increase in GH concentrations after the end of rhIGF-I infusion is consistent with cessation of an inhibitory effect of free IGF-I on GH release.

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