The role of cholinergic tone in modulating the growth hormone response to growth hormone-releasing hormone in normal man.
Growth hormone-releasing hormone (GHRH) increases serum GH levels in a dose-dependent manner. Pyridostigmine (PD), an acetylcholinesterase inhibitor, is able to elicit GH secretion when administered alone and to enhance the GH response to GHRH in normal subjects, probably via a decrease in the hypothalamic release of somatostatin. The aim of the present study was to investigate if an enhancement of the cholinergic tone was able to influence the dose-response relationship between GHRH and GH in normal adult subjects. Six healthy adult volunteers underwent 10 experimental protocols. They were: human GHRH (1-29)NH2, 1 micrograms/kg injected as an intravenous (IV) bolus 60 minutes after (a) PD, 120 mg administered orally, or (b) placebo, two tablets administered orally; GHRH, 0.3 micrograms/kg injected as an IV bolus 60 minutes after (c) PD or (d) placebo; GHRH, 0.1 micrograms/kg injected as an IV bolus 60 minutes after (e) PD or (f) placebo; GHRH, 0.01 micrograms/kg injected as an IV bolus 60 minutes after (g) PD or (h) placebo; saline, 1 mL injected as an IV bolus 60 minutes after (i) PD or (l) placebo. The GH response in placebo-treated subjects was similar after 1 microgram/kg and 0.3 microgram/kg GHRH, while the 0.1 microgram/kg dose elicited a lower response. The 0.01 microgram/kg dose of GHRH did not significantly increase GH levels as compared with saline. After PD, the GH responses to GHRH were greatly enhanced at all doses tested: 1.0, 0.3, and 0.1 microgram/kg GHRH all elicited similar GH responses; the GH response to 0.01 microgram/kg GHRH was lower, but was still higher than that observed after saline.(ABSTRACT TRUNCATED AT 250 WORDS)
Giustina
A
A
Cattedra di Clinica Medica, University of Brescia, Italy.
Bossoni
S
S
Bodini
C
C
Doga
M
M
Girelli
A
A
Buffoli
M G
MG
Schettino
M
M
Wehrenberg
W B
WB
D000328:Adult; D004305:Dose-Response Relationship, Drug; D005260:Female; D013006:Growth Hormone / Q000097:blood / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology*; D006801:Humans; D008297:Male; D010275:Parasympathetic Nervous System / Q000502:physiology*; D010919:Placebos; D011729:Pyridostigmine Bromide / Q000494:pharmacology; D012016:Reference Values
D010919:Placebos; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; D011729:Pyridostigmine Bromide