The late growth hormone rise induced by oral glucose is enhanced by cholinergic stimulation with pyridostigmine in normal subjects.
OBJECTIVE
We have investigated the late GH rise occurring 3-5 hours after oral glucose administration. We have assessed the effect of endogenous cholinergic enhancement with pyridostigmine on the delayed GH rise following oral glucose loading in normal subjects.


METHODS
Placebo or 75 g oral glucose was given to the normal subjects 3 hours before 120 mg oral pyridostigmine or placebo. Four tests were carried out at random. (0 min) + placebo (180 min); test 2: glucose (0 min) + placebo (180 min); test 3: placebo (0 min) + pyridostigmine (180 min); test 4: glucose (0 min) + pyridostigmine (180 min).


METHODS
We studied eight normal subjects (four male and four female), ages 19-29 years, body mass indices 18-22 kg/m2.


METHODS
Plasma glucose and serum GH concentrations were measured for 6 hours after oral glucose or placebo administration.


RESULTS
Pyridostigmine treatment significantly enhanced the GH releasing effect of prior (3 h) oral glucose. Late GH peak obtained by oral glucose loading rose from (mean +/- SEM) 17.4 +/- 4.6 to 37.2 +/- 9.0 mU/l (P < 0.05) after pyridostigmine, while GH peak following placebo plus pyridostigmine was 12.4 +/- 2.0 mU/l (P < 0.05 vs glucose plus pyridostigmine). The analysis of GH area under curves (AUCs) in the second phase of the tests (180-360 min) confirmed that glucose plus pyridostigmine released a greater amount of GH (4128 +/- 764 mU/l/3h) than glucose (1694 +/- 494 mU/l/3h, P < 0.001) or pyridostigmine alone (1292 +/- 150 mU/I/3h, P < 0.001).


CONCLUSIONS
Pyridostigmine, an indirect cholinergic drug likely to inhibit somatostatin secretion from the hypothalamus, enhanced the late GH releasing activity of oral glucose. There is evidence that glucose suppresses plasma GH initially by increasing hypothalamic somatostatin release. This would result in an increase in the pituitary stores of GH. We propose that the delayed GH rise after oral glucose occurs when there is a fall in hypothalamic somatostatinergic tone; this is further reduced by the administration of pyridostigmine. At this time the pituitary stores of GH are released as a consequence of resumption of hypothalamic GHRH activity. This leads to the late GH rise.
Valcavi
R
R
2a Divisione di Medicina Interna, Sezione Endocrino Metabolica Arcispedale S. Maria Nuova, Reggio Emilia, Italy.
Zini
M
M
Davoli
S
S
Portioli
I
I
D000284:Administration, Oral; D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D005260:Female; D005947:Glucose / Q000008:administration & dosage*; D013006:Growth Hormone / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007031:Hypothalamus / Q000187:drug effects; D008297:Male; D011729:Pyridostigmine Bromide / Q000494:pharmacology*; D012636:Secretory Rate / Q000187:drug effects; D013997:Time Factors
D001786:Blood Glucose; D013006:Growth Hormone; D005947:Glucose; D011729:Pyridostigmine Bromide