title: Activation of cholinergic neurotransmission by pyridostigmine reverses the inhibitory effect of hyperglycemia on growth hormone (GH) releasing hormone-induced GH secretion in man: does acute hyperglycemia act through hypothalamic release of somatostatin?
abstract: Acute hyperglycemia blocks growth hormone (GH) secretion in response to provocative stimuli including growth hormone releasing hormone (GHRH) administration. However, the precise mechanism of glucose action is unknown. To determine if enhanced somatostatinergic stimulation accounts for the decreased GH secretion, we studied the effect of enhanced cholinergic tone by pyridostigmine on the hyperglycemia blockade of GH release in 7 normal subjects. Pyridostigmine, an acetylcholinesterase inhibitor, has been postulated as an inhibitor of somatostatin release. Each subject underwent 4 tests with GHRH injection (100 micrograms i.v. at 0 min). In the first (control) test, placebo was administered before GHRH. In the second test, 100 g of glucose was administered p.o. 45 min before GHRH. In the third test, pyridostigmine, 120 mg p.o., was administered 60 min before GHRH, and in the fourth test, pyridostigmine, glucose and GHRH were administered at -60, -45 and 0 min, respectively. GHRH-induced GH secretion of 25.8 +/- 4.5 ng/ml was significantly reduced by previous glucose administration (12.1 +/- 4.5 ng/ml) and significantly potentiated by previous pyridostigmine pretreatment (56.5 +/- 16.8 ng/ml). In the fourth test (pyridostigmine plus glucose plus GHRH) the GH peak of 42.4 +/- 9.2 ng/ml was significantly higher than after GHRH alone and not different to the pyridostigmine-GHRH test. In conclusion, central cholinergic activation by pyridostigmine reversed the hyperglycemic blockade of GHRH-induced GH secretion. In addition, hyperglycemia was unable to reduce the potentiating effect of pyridostigmine on GH secretion elicited by GHRH. Based on the reported actions of pyridostigmine, acute hyperglycemia might act over GH release by inducing hypothalamic somatostatin release.
authors.affiliation: Department of Medicine, General Hospital of Galicia, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Peñalva
authors.forename: B
authors.initials: B
authors.lastname: Burguera
authors.forename: X
authors.initials: X
authors.lastname: Casabiell
authors.forename: J A
authors.initials: JA
authors.lastname: Tresguerres
authors.forename: C
authors.initials: C
authors.lastname: Dieguez
authors.forename: F F
authors.initials: FF
authors.lastname: Casanueva
mesh_terms: D000208:Acute Disease; D000328:Adult; D004357:Drug Synergism; D005947:Glucose / Q000494:pharmacology; D013006:Growth Hormone / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism*; D007031:Hypothalamus / Q000378:metabolism; D008297:Male; D010275:Parasympathetic Nervous System / Q000187:drug effects* / Q000502:physiology; D011729:Pyridostigmine Bromide / Q000494:pharmacology*; D013004:Somatostatin / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects*
chemical_list: D013004:Somatostatin; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; D005947:Glucose; D011729:Pyridostigmine Bromide