Acute hyperglycemia and activation of the beta-adrenergic system exhibit synergistic inhibitory actions on growth hormone (GH) releasing hormone-induced GH release.
OBJECTIVE
Acute hyperglycemia stimulates somatostatin (SRIH) release by the hypothalamus which, in turn, suppresses growth hormone (GH) secretion from the anterior pituitary gland. Although it has been suggested that the cholinergic pathway mediates glucose-induced SRIH release, other regulatory systems have not been examined. Therefore, we investigated whether blocking or activating the beta-adrenergic pathway alters glucose-mediated inhibition of GH release.


METHODS
One set of experiments was performed with a beta-adrenergic antagonist, propranolol, and the other set with a beta-adrenergic agonist, isoproterenol. Each set of experiments was performed in ten healthy subjects and consisted of four tests. Test 1, a 100 microg GHRH bolus i.v. at 0 min; test 2, 100 g glucose orally at -30 min, followed by a 100 microg GHRH bolus at 0 min; test 3, after a 100 microg GHRH bolus i.v. at 0 min, a continuous infusion of propranolol (0.2 mg/kg) or isoproterenol (0.012 microg/kg) was administered between 0 and 120 min; test 4, after a 100 g glucose oral load at -30 min, and a 100 microg GHRH bolus i.v. at 0 min, a continuous infusion of propranolol (0.2 mg/kg) or isoproterenol (0.012 microg/kg) was administered between 0 and 120 min. Blood was drawn every 10 min from -30 min to 120 min to measure GH and glucose concentrations.


RESULTS
Pretreatment with glucose significantly suppressed GHRH-induced GH secretion. Propranolol infusion significantly increased the GHRH-induced GH secretion, but it did not block glucose-induced suppression of GH secretion. Isoproterenol infusion alone significantly suppressed GHRH-induced GH secretion and augmented the inhibitory action of glucose on GH release.


CONCLUSIONS
This study demonstrates that glucose-induced suppression of GHRH-stimulated GH release is independent of beta-adrenergic tone. Since previous data supports a role for SRIH in both glucose and beta-adrenergic suppression of GH release, the current results suggest that subsets of SRIH neurons are differentially responsive to these external cues. Therefore, a combined glucose and isoproterenol test may provide a useful assessment of hypothalamic somatostatinergic activity.
Park
Cheolyoung
C
Department of Internal Medicine, Kyunghee University School of Medicine, #1 Hoiki-dong, Dongdaemun-ku, Seoul 130-071, Korea.
Yang
Inmyung
I
Woo
Jeongtaek
J
Kim
Sungwoon
S
Kim
Jinwoo
J
Kim
Youngseol
Y
Park
Seungjoon
S
D000208:Acute Disease; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage; D000328:Adult; D004357:Drug Synergism; D013007:Growth Hormone-Releasing Hormone / Q000378:metabolism*; D019382:Human Growth Hormone / Q000378:metabolism*; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D007545:Isoproterenol / Q000008:administration & dosage; D008297:Male; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism*; D011433:Propranolol / Q000008:administration & dosage
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D019382:Human Growth Hormone; D013007:Growth Hormone-Releasing Hormone; D011433:Propranolol; D007545:Isoproterenol