Nephrology Dialysis Transplantation, Vol 14, Issue 7 1704-1709, Copyright © 1999 by Oxford University Press
J Diez, P Iglesias, A Aguilera, M Bajo and R Segas
Background: 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. Methods: 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
&mgr;g, 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.
Results: 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 &mgr;g/l)
were similar to those reached by controls (18.0±3.1
&mgr;g/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±3.9
vs 15.4±3.3 &mgr;g/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±3.0 &mgr;g/h/l, P<0.05)
and in control subjects (2.0±0.3 &mgr;g/h/l, P<0.05).
Conclusion: 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. Key words: chronic
renal failure; growth hormone; growth hormone-releasing hormone; peritoneal
dialysis; pirenzepine
ORIGINAL ARTICLES
Effects of cholinergic muscarinic blockade on growth hormone responses to growth hormone-releasing hormone in uraemic patients
Departments of Endocrinology and Nephrology, Hospital La Paz, Madrid, Spain; Corresponding author at: Travesía Téllez 8, 4R, E-28007 Madrid, Spain. E-mail: mibarsd@infomed-dental.com
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