Hyporesponsiveness of the Pituitary to CRH during Slow Wave Sleep Is Not Mimicked by Systemic GHRH

Abstract

During slow wave sleep (SWS) pituitary responsiveness to CRH is reduced. Since GHRH is involved in the promotion of SWS in humans and rats, it was examined whether the blunted CRH-induced ACTH and cortisol release during SWS could be mimicked by systemic GHRH. Young healthy men (n = 7) participated in 4 sleep-endocrine protocols: (A) lights off at 23.00 h, intravenous injection of 50 µg CRH during the first SWS period; (B) lights off at 01.00 h, injection of 100 µg GHRH at 23.00 h, followed by 50 µg CRH at 23.30 h; (C) lights off at 01.00 h, injection of 50 µg CRH at 23.30 h, and (D) lights off at 23.00 h, saline treatment only (= baseline condition). The sleep EEG was recorded during the lights off period and blood samples, collected every 20 min between 22.00 and 07.00 h, were assayed for GH, cortisol and ACTH. There was no significant difference in the sleep-associated GH peak between protocols. Plasma ACTH was significantly higher following CRH administration during wakefulness compared with CRH administration during SWS (protocols B and C vs. A; area under the curve (AUC) 23.00–03.00 h: 9.6 ± 4.8 and 7.3 ± 2.0 vs. 6.1 ± 1.1 ng/ml × min; p < 0.05), while there was no significant difference in plasma ACTH concentration between the baseline condition and protocol A (CRH administration during SWS). Similarly, cortisol was significantly enhanced compared with baseline following CRH during wakefulness only. CRH induced an increase in EEG activity in the sigma frequency range, both when it was administered during wakefulness and SWS, while this effect was reduced by pre-treatment with GHRH. In summary, our data suggest that (1) the blunted CRH-induced release of ACTH and cortisol during SWS is not mimicked by systemic GHRH administration, and (2) CRH enhances sigma EEG activity possibly via modulation of afferent pathways from the median eminence to the thalamus and this effect is reduced by pre-treatment with GHRH.