Short term continuous intravenous infusion of growth hormone (GH) inhibits GH-releasing hormone-induced GH secretion: a time-dependent effect.
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 microgram/kg, iv) was administered 2 h after the start of a 4-h continuous iv infusion of GH (180-micrograms bolus dose, then 3 micrograms/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-micrograms bolus dose, then 3 micrograms/min). During the GH infusions, plasma GH levels reached steady state concentrations in the 9-13 micrograms/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 micrograms.min/L during placebo; P = 0.29], but was significantly inhibited during the 6-h GH infusions (226 +/- 105 micrograms.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 time-dependent 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.
Rosenthal
S M
SM
Department of Pediatrics, University of California, San Francisco 94143.
Kaplan
S L
SL
Grumbach
M M
MM
D000328:Adult; D013006:Growth Hormone / Q000008:administration & dosage* / Q000037:antagonists & inhibitors / Q000378:metabolism; D013007:Growth Hormone-Releasing Hormone / Q000008:administration & dosage* / Q000494:pharmacology; D006801:Humans; D007262:Infusions, Intravenous; D007334:Insulin-Like Growth Factor I / Q000097:blood; D008297:Male; D012636:Secretory Rate / Q000187:drug effects*; D013997:Time Factors
D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone