BLOCKING OF CENTRAL NERVOUS MINERALOCORTICOID RECEPTORS COUNTERACTS INHIBITION OF PITUITARY-ADRENAL ACTIVITY IN HUMAN SLEEP

Pituitary-adrenal activity has been found to be inhibited during early nocturnal sleep in humans. This inhibition was supposed to reflect a regulatory influence of hippocampal cells characterized by the express ion of mineralocorticoid receptors (MR). Pituitary adrenal responsiven ess to bolus injections of CRH (50 mu g) was examined in each of nine healthy men on four occasions: CRH was injected either during early no cturnal sleep or at the same time of night while the subject was kept awake. Both of these conditions were run after pretreatment with the s elective MR antagonist, canrenoate (2 x 200 mg, 0800 and 1700 h, prece ding the experimental night) and after placebo administration. After p lacebo, sleep reduced ACTH and cortisol secretory responses to CRH to about 65% of the size observed during wakefulness (P < 0.05). After ca nrenoate, ACTH and cortisol secretory responses during sleep and wakef ulness did not differ and were comparable with those obtained in place bo-treated subjects during wakefulness. Compared with placebo, canreno ate also distinctly reduced the time spent in slow-wave sleep (P < 0.0 05). The findings confirm an inhibition of pituitary-adrenal responsiv eness during early sleep. The inhibition disappearance after blockage of MR suggests that sleep exerts this influence via central nervous MR -expressing cells. These cells seem to be simultaneously involved in t he generation of slow-wave sleep.