Corticotropin-Releasing Hormone Inhibition of Growth Hormone-Releasing Hormone-Induced Growth Hormone Release in Man*

Abstract

Recent studies in the rat have shown that intracerebroventricular administration of CRH inhibited spontaneous pulsatile GH secretion and prevented GH-releasing hormone (GHRH)-induced GH release. We have studied the effect of CRH on GHRH-induced GH release in man. In the first study, CRH was injected iv at three different doses (100, 50, or 25 micrograms) at 0800 h together with 50 micrograms GHRH in six men and six women. In a second study, 100 micrograms CRH were given iv at 0800 h, 1 h before the administration of 50 micrograms GHRH in five men and five women. Each subject demonstrated a normal GH response after the administration of 50 micrograms GHRH plus saline. All doses of CRH administered simultaneously with GHRH significantly inhibited GHRH-induced GH release in women [peak value +/- SE after GHRH plus saline, 28.9 +/- 2.9 micrograms/L; after GHRH plus 100 micrograms CRH, 9.9 +/- 0.7 micrograms/L (P less than 0.001); after GHRH plus 50 micrograms CRH, 8.7 +/- 0.8 micrograms/L (P less than 0.001); after GHRH plus 25 microgram CRH, 9.5 +/- 1.6 microgram/L (P less than 0.001]). In contrast, in men, while a dose of 100 micrograms CRH was capable of suppressing GHRH-induced GH secretion (peak value +/- SE, 8.1 +/- 0.6 vs. 20 +/- 2.9 micrograms/L; P less than 0.001), no inhibition was observed after 50- and 25-micrograms doses. When 100 micrograms CRH were injected 1 h before the administration of 50 micrograms GHRH, it strongly inhibited GHRH-induced GH secretion in both men (peak value +/- SE, 6.2 +/- 2.8 vs. 24.6 +/- 5.9 micrograms/L; P less than 0.02) and women (peak value +/- SE, 14.2 +/- 4.5 vs. 37.8 +/- 6.7 micrograms/L; P less than 0.005), and this inhibition lasted up to 2 h post-CRH administration. These results demonstrate that CRH is capable of inhibiting GHRH-induced GH release in both men and women. Furthermore, the findings suggest that a sexual dimorphism in the neuroregulation of GH secretion may be present in man. In view of the inhibitory action of CRH on GH secretion, simultaneous administration of CRH and GHRH for testing should be avoided in clinical practice.