Effects of cholinergic muscarinic antagonist pirenzepine on GH response to GHRH 1-40 in patients with anorexia nervosa.

Abstract

The effects of cholinergic muscarinic receptor antagonist pirenzepine on the GHRH-induced GH release were studied in 10 adolescent females with anorexia nervosa at different stages of the disease, in 5 adolescent females with eating disorders and in 5 normal adolescents. The patients were characterized according to psychological (DSM III-R), endocrinological (GnRH test), nutritional (Somatomedin-C, T3), and clinical (% IBW, duration of the amenorrhoea) criteria. On two separate occasions, each subject received an i.v. bolus injection of GHRH 1-40 (1 microgram/kg) alone or preceded by pirenzepine (0.6 mg/kg i.v. 5 min before GHRH 1-40). GHRH 1-40 injection induced a significantly (P less than 0.05) higher GH increase in the patients with anorexia nervosa at the acute stage as compared with the controls. Pirenzepine did not abolish opportunely the exaggerated GH response to GHRH 1-40 in anorectic patients at the acute stage unlike the control, who showed the blockade of GHRH-induced GH release by the cholinergic muscarinic antagonist (P less than 0.05). The anorectic adolescents at the non acute stage and the adolescents with eating disorders showed varying reductions of GH response; however, pirenzepine produced a blunted suppression of GHRH-induced GH increase as compared to the controls, which was not statistically significant. Somatomedin-C values were significantly (P less than 0.05) lower in anorectic patients at the acute stage as compared with controls. The abnormal activity of cholinergic system in anorectic patients, as our data show, could induce the GH hypersecretion through an inhibitory influence on the somatostatinergic function. The reduced somatomedin-C levels, a specific malnutrition index in anorectic patients, produce a modified feed-back on the hypothalamic site (somatostatin) and/or directly on the pituitary, following the GH hypersecretion.