Effect of oral glucose administration on plasma growth hormone-releasing hormone (GHRH)-like immunoreactivity levels in normal subjects and patients with idiopathic GH deficiency: evidence that GHRH is released not only from the hypothalamus but also from extrahypothalamic tissue.

Abstract

Using a specific and sensitive RIA for GH-releasing hormone (GHRH), we examined the effect of oral administration of 75 g glucose on peripheral plasma GHRH-like immunoreactivity (GHRH-LI) in normal subjects (n = 12) and patients with idiopathic GH deficiency (IGHD) (n = 6). The normal subjects had two peaks of plasma GHRH-LI after oral glucose administration. The initial peak GHRH-LI levels occurred 30-150 min after glucose ingestion and corresponded to an increase in blood glucose. The increment in plasma GHRH-LI levels 30 min after glucose ingestion [7.4 +/- 2.4 (+/- SEM) pg/ml] was significantly higher (P less than 0.05) than that during a control study. Second peaks in plasma GHRH-LI occurred 3.5-6 h after glucose ingestion, and the mean increment 5 h after glucose ingestion was 9.4 +/- 2.4 pg/ml. This second rise of plasma GHRH-LI coincided with a significant increase in plasma GH after reactive hypoglycemia. This second GHRH-LI peak and the rise of plasma GH after hypoglycemia were absent in patients with IGHD, whereas the first peak of plasma GHRH-LI appeared shortly after glucose ingestion in these patients as well as in normal subjects. In addition, hypoglycemia produced by iv injection of regular insulin (0.1 U/kg) was not accompanied by increases in plasma GHRH-LI and GH levels in patients with IGHD, whereas insulin-induced hypoglycemia resulted in significant elevations of both plasma GHRH-LI and GH levels in normal subjects. These findings suggest that peripheral plasma GHRH-LI is derived from the hypothalamus as well as from an extrahypothalamic source(s); extrahypothalamic GHRH is released shortly after glucose ingestion; and secretion of GHRH from the hypothalamus is stimulated by hypoglycemia.