Effects of cholinergic blockade on nocturnal thyrotropin and growth hormone (GH) secretion in type I diabetes mellitus: further evidence supporting somatostatin's involvement in GH suppression

To investigate the influence of cholinergic pathways on somatostatin (SS) tone in type I diabetes mellitus, we studied the effect of the muscarinic receptor antagonist pirenzepine ([PZP] 100 mg orally) on spontaneous nocturnal growth hormone (GH) and thyrotropin (TSH) secretion and on their response to GH-releasing hormone (GHRH) in the morning in a group of nine insulin-dependent diabetic patients with poor diabetic control.

When the nocturnal period was divided into two phases (11:00 PM to 2:30 AM and 3:00 AM to 6:00 AM), both GH and TSH mean concentrations during the first phase were higher than those seen in the second half of the night following placebo administration (GH, 13.4 +/- 1.1 v 4.15 +/- 0.9 ng/mL, P < .001; TSH, 1.9 +/- 0.21 v 1.57 +/- 0.1 microU/mL, P < .05). Pretreatment with PZP induced a significant reduction of GH secretion (3.17 +/- 1.1 v 13.4 +/- 1.1 ng/mL, P < .001) and TSH secretion (1.61 +/- 0.21 microU/mL, P < .05) in the first phase of the night, accounting for a 64% and 11% reduction in the GH and TSH nocturnal peak, respectively. PZP reduced the GH response to GHRH in the morning (17.9 +/- 2.7 v 36.7 +/- 6.3 ng/mL, P < .05), but did not induce any change in TSH values at that time. A positive relationship (r = .73, P < .01) was observed between the percent reduction of the GH response to GHRH and that of the nocturnal GH peak following PZP administration. PZP caused a significant reduction in glucose levels during the second phase of the night (6.4 +/- 0.92 v 9.81 +/- 0.85 mmol/L, P < .05).

These results demonstrate that administration of PZP reduces GH and TSH secretion, providing further support for the involvement of SS in the inhibition of GH secretion induced by cholinergic antagonists in type I diabetics. The inhibitory effect of PZP on GHRH-induced GH secretion may help to predict nocturnal GH behavior following administration of the drug.

CITA DEL ARTÍCULO  Metabolism. 1997 Nov;46(11):1305-11