In vivo evidence that preexposure to somatostatin enhances growth hormone responsiveness to growth hormone-releasing factor

The ultradian rhythm of growth hormone (GH) secretion from the anterior pituitary gland is ultimately controlled by the complex interaction of two hypothalamic hormones, a stimulatory GH-releasing factor (GRF), and an inhibitory hormone, somatostatin (SRIF).In the present study, we used the long-acting SRIF analog, octreotide, as a probe in both the normal and mutant dwarf rat to (1) further clarify the temporal nature of the SRIF/GRF interplay in GH regulation in vivo, and (2) define possible mechanisms of action of SRIF in generating the ultradian rhythm of GH secretion characteristic of the normal male rat. Administration of octreotide to free-moving, chronically cannulated adult male rats resulted in an almost complete obliteration of spontaneous GH pulses for 3 hours, with gradual recovery observed 3-6 hours after injection. Rats pretreated with octreotide i.v. and subsequently challenged with GRF exhibited reduced GH responsiveness to exogenous GRF at 1 hour post treatment. In contrast, preexposure to octreotide for 3 hours resulted in a 2-3 fold enhancement in GH responsiveness to GRF compared to controls pretreated with normal saline to normal saline-pretreated controls. In contrast, we report that preexposure to octreotide (n = 6) in a strain of dwarf rats, which shows a selective reduction in pituitary GH synthesis and storage, failed to significantly enhance GRF-induced GH release.Our findings suggest that SRIF pretreatment promotes the accumulation of pituitary GH stores in a readily releasable pool so that subsequent GRF challenges can exert an accentuated effect on pituitary somatotrophs. (Abstract shortened by UMI.