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Short Term Continuous Intravenous Infusion of Growth Hormone (GH) Inhibits GH-Releasing Hormone-Induced GH Secretion: A Time-Dependent Effect^*

Department of Pediatrics, University of California San Francisco, California 94143

Address requests for reprints to: Stephen M. Rosenthal, M.D., Box 0434, University of California, San Francisco, California 94143.

We previously reported that GH secretion evoked by GHRH is inhibited after 5 days of treatment with im GH. This impaired pituitary response was associated with a significant increase in the serum concentration of insulin-like growth factor I (IGF-I). To dissociate the possible effects of circulating IGF-I from other effects of GH on the pituitary response to GHRH, we carried out the following study in eight normal men. A bolus injection of GHRH (1 µg/kg, iv) was administered 2 h after the start of a 4-h continuous iv infusion of GH (180-µg bolus dose, then 3 µg/min in 150 mmol/L NaCl) or placebo (150 mmol/L NaCl). In addition, a similar injection of GHRH was given 4 h after the start of a 6-h continuous iv GH infusion (180-µg bolus dose, then 3 µg/min). During the GH infusions, plasma GH levels reached steady state concentrations in the 9–13 µg/L range. The mean GHRH-induced GH response was not significantly blunted during the 4-h infusions of GH 724 ± 163 (±SE) vs. 1184 ± 373 µg·min/L during placebo; P = 0.29], but was significantly inhibited during the 6-h GH infusions 226 ± 105 µg·min/L; P = 0.04 vs. control). Serum IGF-I or plasma glucose did not change significantly throughout the GH infusions. During the 6-h GH infusions, plasma FFA increased to levels significantly above basal values during the last 3 h of the 6-h infusion. These results indicate that short term GH infusion inhibits the plasma GH response to GHRH in a timedependent manner. The inhibition is not due to changes in circulating IGF-I and glucose concentrations. Fluctuations in hypothalamic somatostatin secretion, changes in lipid or other GH-dependent metabolites, paracrine effects of IGF-I, or a direct effect of GH itself may cause the impaired pituitary responsiveness during short term iv GH infusion.

^* This work was supported in part by a grant from the NICHHD, NIH (R01-HD-02335), and the NIH, Pediatric Clinical Research Center (RR-01271). Presented in part at the 68th Annual Meeting of The Endocrine Society, Anaheim, CA, 1986.

Received August 25, 1988.

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