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 microgram/kg iv, with and without administration of Pz, 40 mg 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 cholinergic-somatostatinergic dysfunction in acromegaly.
Subject(s)
Acromegaly/blood , Acromegaly/surgery , Cholinergic Fibers/physiology , Growth Hormone/blood , Pituitary Gland/metabolism , Adult , Cholinergic Fibers/ultrastructure , Female , Growth Hormone-Releasing Hormone/pharmacology , Humans , Male , Middle Aged , Neurotransmitter Agents/pharmacology , Pirenzepine/pharmacology , Pituitary Gland/surgery , Receptors, Muscarinic/analysis , Receptors, Muscarinic/drug effectsABSTRACT
In order to ascertain if pirenzepine (Pz), an antimuscarinic drug, could inhibit GH secretion in acromegaly, 8 patients were submitted to 3 successive treatment courses of 9 days each: Pz, bromocriptine (BRC) and Pz plus BRC. No change in basal levels of GH after Pz administration was seen, but its reduction (p less than 0.05) by BRC was observed. Pz plus BRC did not improve this response. None of these drugs abolished the paradoxical GH response to TRH. In 7 normal controls, Pz suppressed the GH responsiveness to GHRH (p less than 0.001), but not in acromegalic patients. BRC, instead, blunted this response. In conclusion, cholinergic control of GH secretion is altered in acromegaly. Pz, either when administered alone or associated with BRC, is not useful for the treatment of this disease.
Subject(s)
Acromegaly/physiopathology , Bromocriptine/pharmacology , Growth Hormone-Releasing Hormone , Growth Hormone/metabolism , Pirenzepine/pharmacology , Thyrotropin-Releasing Hormone , Acromegaly/drug therapy , Adult , Bromocriptine/administration & dosage , Bromocriptine/therapeutic use , Female , Humans , Male , Middle Aged , Pirenzepine/administration & dosage , Pirenzepine/therapeutic useABSTRACT
The effects of dietary manipulation (low- or high-carbohydrate) on performance of a short-duration exercise were studied with endurance- and intermittent-trained athletes. Eight subjects performed a depletion drill of 10 one minute workbouts at 7 W/kg and 85 rpm on a cycle ergometer. The subjects followed a dietary regimen of three days on a low-carbohydrate diet followed by three days on a high-carbohydrate diet. Muscle biopsy samples were taken immediately prior to and immediately after the testing sessions. Dietary manipulation did not affect resting muscle glycogen levels. However, subjects accustomed to continuous training regimens used less glycogen, produced less muscle lactate and exercised longer than subjects accustomed to intermittent training programs. These biochemical changes appeared to be related to the fibre type distribution and the training background of the athletes.
