Cholinergic muscarinic receptor blockade with pirenzepine abolishes slow wave sleep-related growth hormone release in normal adult males.

Abstract

Cholinergic pathways play an important role in the regulation of GH secretion from the anterior pituitary gland, and in this study we have investigated whether cholinergic muscarinic receptor blockade with pirenzepine displayed any inhibitory action on slow wave sleep-related GH release in normal subjects. Six adult males (ages 24-37 years) were studied in a randomized order and fasted from 1800 h on each study day. All subjects showed episodes of slow wave sleep on each occasion and this was followed by peaks of GH release when placebo alone was administered (range of GH peaks 4-50 mU/l). In contrast, pirenzepine treatment (100 mg p.o. at 2200 and 2400 h) completely abolished nocturnal GH release in each individual without altering the occurrence of slow wave sleep itself. These data demonstrate clearly that cholinergic muscarinic receptor blockade completely abolishes slow wave sleep-related GH release in normal adult subjects. Because of the striking effects it is reasonable to conclude that acetylcholine plays an important stimulatory role in mediating slow wave sleep-related GH release. This finding may have investigational and therapeutic applications in young patients with Type 1 diabetes mellitus since GH is implicated in some acute metabolic and chronic microvascular complications of this disease.