Pyridostigmine does not reverse dexamethasone-induced growth hormone inhibition.
Glucocorticoids inhibit the growth hormone (GH) response to a variety of stimuli, including GH-releasing hormone (GHRH) in vivo, but they increase GHRH-stimulated GH secretion when added, in vitro, to animal and human pituitary cells. This discrepancy has led to the hypothesis that glucocorticoids act in vivo by increasing somatostatin secretion from the hypothalamus. To examine this hypothesis, we used a cholinergic drug, pyridostigmine (PD), which reduces hypothalamic somatostatin secretion. Eight normal volunteers were studied. They underwent four tests: (1) GHRH test; (2) Dex + GHRH (GHRH test after treatment the night before, with dexamethasone (Dex)); (3) PD + GHRH; (4) Dex + PD + GHRH. Dex significantly inhibited the GH response to GHRH expressed as area under the GH/time curve (AUC, microgram/1/min) (mean +/- SEM = 895.2 +/- 196.6 vs 1970.9 +/- 600.1, P less than 0.05). PD significantly increased the AUC of GH secretion in PD + GHRH compared with GHRH alone (3541.2 +/- 571.3 vs 1970.9 +/- 600.1, P less than 0.01) but by no means restored completely the normal GH response to GHRH, when given to Dex-pretreated subjects. Furthermore, the mean AUC of Dex + PD + GHRH was significantly lower than that of PD + GHRH (1621.7 +/- 500.6 vs 3541.2 +/- 571.3, P less than 0.01), demonstrating that Dex continues to exert its inhibitory effect on GH secretion in the presence of PD. These results suggest that glucocorticoid-induced GH inhibition does not act solely through an increase in hypothalamic somatostatin secretion.
del Balzo
P
P
Division of Pediatric Endocrinology, New York Hospital-Cornell University, Medical College, New York.
Salvatori
R
R
Cappa
M
M
Gertner
J M
JM
D000328:Adult; D003864:Depression, Chemical; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D013006:Growth Hormone / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology; D006801:Humans; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D011729:Pyridostigmine Bromide / Q000494:pharmacology*; D013004:Somatostatin / Q000378:metabolism*
D013004:Somatostatin; D003907:Dexamethasone; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; D011729:Pyridostigmine Bromide