Pyridostigmine partially reverses dexamethasone-induced inhibition of the growth hormone response to growth hormone-releasing hormone.
The GH response to insulin-induced hypoglycaemia and growth hormone-releasing hormone (GHRH) has been shown to be impaired in subjects with Cushing's syndrome and in healthy volunteers given oral glucocorticoids. Pyridostigmine is an anticholinesterase that stimulates GH secretion, probably by inhibition of hypothalamic somatostatin secretion. This work was designed to study the site of action of glucocorticoids in inhibiting the secretion of GH. Eight healthy male volunteers were studied on three occasions in random order. They took 2 mg oral dexamethasone or placebo at precisely 6-hourly intervals for 48 h before receiving 120 mg oral pyridostigmine or placebo, followed 60 min later by GHRH (100 micrograms) i.v. Samples for measuring GH were obtained at 15 min intervals for 2 h. The 'area under the curve' (AUC) for each of the treatments was significantly different: dexamethasone-pyridostigmine-GHRH (mean +/- S.E.M., 1938 +/- 631 mU/min per l), dexamethasone-placebo-GHRH (634 +/- 211) and placebo-placebo-GHRH (4267 +/- 1183) (P < 0.02, Wilcoxon test). In conclusion, dexamethasone given for 48 h significantly inhibited the AUC for GH following treatment with GHRH. However, pretreatment with pyridostigmine significantly reversed the inhibition although this was still partial. Our data suggested that this short-term suppressive effect of dexamethasone was independent of GHRH, and most probably relates to stimulation of the release of somatostatin.
Department of Endocrinology, St Bartholomew's Hospital, West Smithfield, London, U.K.
P J
PJ
Trainer
J M
JM
Kirk
M O
MO
Savage
A B
AB
Grossman
G M
GM
Besser
D003864:Depression, Chemical; D003907:Dexamethasone / Q000494:pharmacology*; D013006:Growth Hormone / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D015592:Immunoradiometric Assay; D008297:Male; D011729:Pyridostigmine Bromide / Q000494:pharmacology*; D012636:Secretory Rate / Q000187:drug effects; D013004:Somatostatin / Q000494:pharmacology*
D013004:Somatostatin; D003907:Dexamethasone; D013006:Growth Hormone; D011729:Pyridostigmine Bromide