Hyporesponsiveness of the pituitary to CRH during slow wave sleep is not mimicked by systemic GHRH

During slow wave sleep (SWS) pituitary responsiveness to CRH is reduced. Si nce GHRH is involved in the promotion of SWS in humans and rats, it was exa mined 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 inje ction of 50 mu g CRH during the first SWS period; (B) lights off at 01.00 h , injection of 100 mu g GHRH at 23.00 h, followed by 50 mu g CRH at 23.30 h ; (C) lights off at 01.00 h, injection of 50 mu g CRH at 23.30 h, and (D) l ights off at 23.00 h, saline treatment only (= baseline condition). The sle ep EEG was recorded during the lights off period and blood samples, collect ed every 20 min between 22.00 and 07.00 h, were assayed for GH, cortisol an d ACTH. There was no significant difference in the sleep-associated GH peak between protocols. Plasma ACTH was significantly higher following CRH admi nistration 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 x min; p < 0.05), while there was no significant difference in plasma ACTH concentration between the baselin e condition and protocol A (CRH administration during SWS). Similarly, cort isol was significantly enhanced compared with baseline following CRH during wakefulness only. CRH induced an increase in EEG activity in the sigma fre quency range, both when it was administered during wakefulness and SWS, whi le 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 duri ng SWS is not mimicked by systemic GHRH administration, and (2) CRH enhance s 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.