Acute hyperglycemia and activation of the beta-adrenergic system exhibit synergistic inhibitory actions on growth hormone (GH) releasing hormone-induced GH release

Abstract

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 b-adrenergic pathway alters glucose-mediated inhibition of GH release. Design and methods: One set of experiments was performed with a b-adrenergic antagonist, propranolol, and the other set with a b-adrenergic agonist, isoproterenol. Each set of experiments was performed in ten healthy subjects and consisted of four tests. Test 1, a 100 mg GHRH bolus i.v. at 0 min; test 2, 100 g glucose orally at 2 30 min, followed by a 100 mg GHRH bolus at 0 min; test 3, after a 100 mg GHRH bolus i.v. at 0 min, a continuous infusion of propranolol (0.2 mg/kg) or isoproterenol (0.012 mg/kg) was administered between 0 and 120 min; test 4, after a 100 g glucose oral load at 230 min, and a 100 mg GHRH bolus i.v. at 0 min, a continuous infusion of propranolol (0.2 mg/kg) or isoproterenol (0.012 mg/kg) was administered between 0 and 120 min. Blood was drawn every 10 min from 2 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. Conclusion: This study demonstrates that glucose-induced suppression of GHRH-stimulated GH release is independent of b-adrenergic tone. Since previous data supports a role for SRIH in both glucose and b-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.

Acute Hyperglycemia and Activation of the .BETA.-Adrenergic System do not Exhibit Synergistic Inhibitory Actions on Thyrotropin-releasing Hormone (TRH)-induced Thyroid Stimulating Hormone (TSH) Secretion

“…However, there was no further suppressive effect on TSH secretion by the combined stimulation of glucose and isoproterenol. These results are in contrast to the effects of glucose and isoproterenol on GHRH-induced GH secretion where the degree of suppression induced by combined glucose and isoproterenol treatment was significantly higher than that achieved by glucose and isoproterenol alone [10]. This discrepancy could be attributed to the differences in responsiveness of GH and TSH to hypothalamic SRIH.…”

“…Our laboratory, as well as others, has observed that both of these stimuli block GHRH-induced GH release [10][11][12][13]. Recently we have reported that the degree of suppression of the GH response to GHRH, initiated by glucose and the badrenergic agonist, isoproterenol, was comparable, while the combined effects were significantly higher than that achieved by glucose and isoproterenol alone [10]. In addition, propranolol, a b-adrenergic antagonist was not able to block glucose-induced suppression of GHRH-stimulated GH release.…”

“…On the other hand, several studies have used agents thought to enhance SRIH release which include acute hyperglycemia [5,6] and b-adrenergic agonists [7][8][9]. Our laboratory, as well as others, has observed that both of these stimuli block GHRH-induced GH release [10][11][12][13]. Recently we have reported that the degree of suppression of the GH response to GHRH, initiated by glucose and the badrenergic agonist, isoproterenol, was comparable, while the combined effects were significantly higher than that achieved by glucose and isoproterenol alone [10].…”

Long‐term β‐adrenergic receptor blockade increases levels of the most mature thymocyte subsets in aged rats

“…Furthermore, since P is known to: i) traverse the blood-brain barrier [35] and ii) affect the release of several hypothalamic releasing/inhibiting hormones and consequently the secretion of several pituitary hormones which may directly and/or indirectly, via hormones from their target glands in the periphery, [49][50][51] modulate T-cell differentiation/maturation [52], centrally-regulated mechanisms may mediate some of the observed effects of P in thymi.…”

Change in Somatostatinergic Tone of Acromegalic Patients according to the Size of Growth Hormone-Producing Pituitary Tumors

“…All of these tests should inevitably accompany a change of SST secondary to either the change in glucose levels or the action of somatostatin analogues. Rapid inhibitory effect of hyperglycemia upon GH secretion may be due to somatostatin from hypothalamus (5), and it has been also suggested that this somatostatin release accompanies the modulation of SST (6). Therefore, the change in SST can be regarded as an intermediate link between glucose and GH secretion, and integrated analysis of the results of these tests could be a practical tool to evaluate SST in pituitary adenomas.…”