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.

Cholinergic Enhancement by Pyridostigmine Potentiates Spontaneous Diurnal but not Nocturnal Growth Hormone Secretion in Short Children

“…On the other hand, it would seem from our findings that the cholinergic tone is already maximally stimulated during the night hours. This view is inferentialiy supported by the observations that the cholinergic system plays a key role in generating both REM and slow wave sleep phase in mammals' sleep cycle [1,15,21], which are those related to the initial surge of GH secretion [2.3], More direct evidence for the existence of a strict functional relationship between cholinergic function and the nocturnal GH surge stems from the ability of cholinergic antagonists to completely abolish it 110, 16,18,26], Basing on the foregoing we would speculate that a reduced somatostatinergic tone during the night could be due to a spontaneously increased cholinergic tone.…”

Neuronal M 3 muscarinic acetylcholine receptors are essential for somatotroph proliferation and normal somatic growth

“…Pharmacological studies suggest that central muscarinic cholinergic pathways play a role in stimulating GH release in experimental animals and humans (1)(2)(3)(4)(5)(6)(7)(8)(9). The identification of the molecular pathways and the specific muscarinic ACh receptor (mAChR) subtypes involved in mediating these responses should be of considerable potential therapeutic interest.…”

Simultaneous stimulation of slow-wave sleep and growth hormone secretion by gamma-hydroxybutyrate in normal young Men.

“…Available evidence suggests that nocturnal GH secretion is controlled primarily by growth hormone-releasing hormone (GHRH) release (5). Because GH secretion is also under inhibitory control by somatostastin, variability of somatostatinergic tone may underlie dissociations between SW sleep and nocturnal GH release (6)(7)(8)(9). While such dissociations are observed frequently during late sleep, a large pulse of GH secretion occurs during the first SW period Ͼ 90% of the time and there is a quantitative relationship between the duration of SW stages and the simultaneous amount of GH secreted (10).…”