The role of cholinergic tone in modulating the growth hormone response to growth hormone-releasing hormone in normal man

Abstract

Growth hormone-releasing hormone (GHRH) increases serum GH levels in a dose-dependent manner. Pyridostigmine (PD), an acetylcholinesterase inhibitor, is able to elicit GH secretion when administered alone and to enhance the GH response to GHRH in normal subjects, probably via a decrease in the hypothalamic release of somatostatin. The aim of the present study was to investigate if an enhancement of the cholinergic tone was able to influence the dose-response relationship between GHRH and GH in normal adult subjects. Six healthy adult volunteers underwent 10 experimental protocols. They were: human GHRH (1–29)NH 2, 1 μg/kg injected as an intravenous (IV) bolus 60 minutes after (a) PD, 120 mg administered orally, or (b) placebo, two tablets administered orally; GHRH, 0.3 μg/kg injected as an IV bolus 60 minutes after (c) PD or (d) placebo; GHRH, 0.1 μg/kg injected as an IV bolus 60 minutes after (e) PD or (f) placebo; GHRH, 0.01 μg/kg injected as an IV bolus 60 minutes after (g) PD or (h) placebo; saline, 1 mL injected as an IV bolus 60 minutes after (i) PD or (l) placebo. The GH response in placebo-treated subjects was similar after 1 μg/kg and 0.3 μg/kg GHRH, while the 0.1 μg/kg dose elicited a lower response. The 0.01 μg/kg dose of GHRH did not significantly increase GH levels as compared with saline. After PD, the GH responses to GHRH were greatly enhanced at all doses tested: 1.0, 0.3, and 0.1 μg/kg GHRH all elicited similar GH responses; the GH response to 0.01 μg/kg GHRH was lower, but was still higher than that observed after saline. We conclude that the endogenous somatostatin tone is a significant factor in modulating the dose-response relationship of GHRH-induced GH secretion in normal man.