Differential effect of insulin-like growth factor-1 and growth hormone on hypothalamic regulation of growth hormone secretion in the rat.

Pharmacological administration of either growth hormone (GH) or insulin-like growth factor 1 (IGF-1) were reported to inhibit endogenous GH release in humans and in the laboratory animal. We have evaluated the short-term differential mechanisms whereby the two hormones affect hypothalamic regulation of GH secretion. Wistar male rats (90 days old) were injected i.p. with either GH (recombinant GH NIAMDD, Baltimore, MD, USA), rIGF-1 (Fujisawa Pharmaceutical Co. Ltd., Osaka, Japan) or saline. Animals were sacrificed at 15, 30, 60 and 120 minutes following injection. Hypothalami were dissected and extracted immediately and the levels of growth hormone-releasing hormone (GHRH) and somatostatin were determined using specific antisera. Trunk blood was collected for GH and IGF-1 determination by RIA. Administration of IGF-1 or GH markedly decreased hypothalamic somatostatin stores by 77% and 54% respectively, within 15 minutes. Concomitantly, the wide range of GH levels found in the control group was reduced in the IGF-1 treated group suggesting that the pulsatile pattern of GH secretion was suppressed. Growth hormone administration induced an increase in hypothalamic GHRH stores (60% at 120 minutes). During this period serum IGF-1 levels were not altered. It is suggested that short term modulation of hypothalamic neurohormones by GH and IGF-1 is mediated by rapid stimulation of somatostatin release by both hormones, and inhibition of GHRH release is induced only by GH.