CORTICOTROPIN-RELEASING HORMONE INHIBITION OF GROWTH HORMONE-RELEASING HORMONE-INDUCED GROWTH-HORMONE RELEASE IN MAN

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 μg) at 0800 h together with 50 μg GHRH in six men and six women. In a second study, 100 μg CRH were given iv at 0800 h, 1 h before the administration of 50 μg GHRH in five men and five women. Each subject demonstrated a normal GH response after the administration of 50 μg 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 μg/L; after GHRH plus 100 μg CRH 9.9 ± 0.7 μg/L (P <0.001); after GHRH plus 50 μg CRH, 8.7 ± 0.8 μg/L (P <0.001); after GHRH plus 25 μg CRH, 9.5 ± 1.6 μg/L (P <0.001)]. In contrast, in men, whil a dose of 100 μg CRH was capable of suppressing GHRH-induced GH secretion (peak value ± SE, 8.1 ± 0.6 vs. 20 ± 2.9 μg/L; P <0.001), no inhibition was observed after 50- and 25-μg doses. When 100 μg CRH were injected 1 h before the administration of 50 μg GHRH, it strongly inhibited GHRH-induced Gh secretion in both men (peak value ± SE, 6.2 ± 2.8 vs. 24.6 ± 5.9 μg/L; P <0.02) and women (peak value ± SE, 14.2 ± 4.5 vs. 37.8 ± 6.7 μg/L; P <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.