Effects of cholinergic muscarinic blockade on growth hormone responses to growth hormone-releasing hormone in uraemic patients.

Abstract

Several alterations in growth hormone (GH) secretion have been reported in patients with chronic renal insufficiency. However, cholinergic modulation of somatotopic cell function has not been fully clarified in uraemic patients. To gain further insight into the disrupted mechanism of GH regulation in chronic renal failure, we investigated whether the blockade of cholinergic muscarinic receptor with pirenzepine could modify the response of GH to its physiological releasing hormone. Eight uraemic male patients on peritoneal dialysis and six normal controls were studied. All subjects underwent two endocrine tests in random order. In one of them placebo was administered 60 min before the injection of GH-releasing hormone (GHRH, 100 microg, i.v. in bolus at 0 min). In another the muscarinic blocking agent pirenzepine, 100 mg p.o., was administered at that time. Blood samples for GH were collected at -60, 0, 15, 30, 45, 60 and 90 min. Baseline plasma GH concentrations were similar in patients and controls. GH responses to GHRH were characterized by great interindividual variability in uraemic patients with regard to the amount and the time to maximal peak. In the placebo plus GHRH test, the maximum GH concentrations in patients (14.0 +/- 3.2 microg/l) were similar to those reached by controls (18.0 +/- 3.1 microg/l), although GH secretion was more sustained in patients. The area under the secretory curve (AUC) of GH secretion in patients was also similar to that found in controls (14.4 +/- 2.9 vs 15.4 +/- 3.3 microg/h/l). When subjects were given pirenzepine before GHRH injection an abolishment of GHRH-induced GH release was observed in all controls and in all but one of the uraemic patients. The AUC of GH secretion was, therefore, significantly reduced both in uraemic patients (4.1 +/- 2.0 microg/h/l, P<0.05) and in control subjects (2.0 +/- 0.3 microg/h/l, P<0.05). These results suggest that GH secretion in uraemic patients is modulated, at least in part, by a cholinergic mechanism. The muscarinic blockade, possibly acting via an increase in somatostatin release, is able to inhibit GH release in response to direct pituitary stimulation with GHRH.