Cholinergic modulation of GH secretion in acromegalic patients before and after pituitary surgery

Abstract

Cholinergic neurotransmission exerts a physiological control on GH secretion. Pirenzepine (Pz), an antagonist of muscarinic receptors, by enhancing hypothalamic somatostatin release, inhibits stimulated GH secretion in normal subjects but not in acromegalic patients. To address the hypothesis that a feedback effect of GH hypersecretion can be involved in this condition, GH responses to GHRH 1–29, 1 μg/kg iv, with and without administration of Pz, 40mg iv before tests, were investigated in eight acromegalic patients, before and 20–30 days after transsphenoidal adenomectomy. Pz diminished (p<0.001) the incremental area under the curve (AUC) of GH responses to GHRH in seven normal controls. In contrast, GHRH responsiveness in untreated acromegalic patients was not affected by Pz. Postoperative basal GH levels decreased by 62.4±14.9% (p<0.01). Pz inhibited GH responses to GHRH (p<0.01). Furthermore, a direct relationship (r = 0.73, p<0.01) between basal concentrations and the AUC of GH responses following Pz plus GHRH-test was found. The finding that muscarinic receptor activity recovered after the reduction of serum GH basal levels by pituitary surgery lends support to the proposed pathophysiological role of GH excess as a possible determinant factor in cholinergicsomatostatinergic dysfunction in acromegaly.