Changes of nocturnal hormone secretion and sleep electroencephalogram after pituitary adenylate cyclase activating peptide (PACAP) in normal young men

Abstract

Pituitary adenylate cyclase activating peptide (PACAP) is involved in autonomous regulation including time keeping by its action on the suprachiasmatic nucleus (SCN), on energy metabolism, transmitter release, and on the secretion of growth hormone (GH), corticotropin (ACTH) and prolactin. In rats PACAP promotes rapid-eye-movement sleep. The effects of PACAP on sleep and nocturnal hormone secretion are unknown. We compared the effects of intravenously administered PACAP to that of placebo in 8 young healthy male subjects. PACAP-38 in a concentration of 4×12.5µg was administered in a pulsatile fashion hourly between 22.00h and 01.00h via long catheter. Sleep electroencephalogram (EEG) was recorded from 23.00h to 10.00h, which was also the time, when the subjects were allowed to sleep. Blood samples were taken every 20 minutes between 22.00h and 07.00h for the determination of cortisol, GH and prolactin. PACAP administration induced no changes in the macro-sleep structure of sleep EEG as assessed by visual scoring. EEG spectral analysis revealed a significant reduction in the theta frequency range in the first 4 hour interval and of the spindle frequency range in the second 4 hour interval of the registration period. This was accompanied with an increase in the time constant τ of the physiological EEG delta-power decline in the course of the night [mean (standard deviation) 339 (75)min after placebo versus 558 (326)], i.e. a less pronounced dynamics of the reduction of delta power with time. This was accompanied by a trend (p<0.1) of a decreased prolactin secretion in the first 4 hour period of the night. No other changes in endocrine secretion were observed. We suggest that PACAP leads to a reduction of the dynamics of homeostatic sleep regulation and prolactin secretion. Both effects are opposite to those seen after sleep-deprivation but similar to the changes after napping, i.e. a reduced sleep propensity. This implies that PACAP might be involved in homeostatic sleep regulation.