Growth hormone releasing hormone 1‐44 NH2 and 1‐40 OH levels in normal subjects during growth hormone stimulation tests

Abstract
Little is known about the relative circulating concentrations of growth hormone releasing hormone (GHRH) 1-44 NH2 and 1-40 OH in response to dynamic GH stimulation. We therefore studied the concentrations of growth hormone-releasing hormone (GHRH) 1-44 NH2 and 1-40 OH in the peripheral plasma of normal male subjects during GH stimulation tests. Tests were performed at 0900 h after an overnight fast. Stimulation tests, commenced at 0 minutes, included alpha-adrenergic activation with adrenaline (10 micrograms/min from 0 to 30 minutes) following beta-blockade with propranolol (1.5 mg/min from -10 to 0 minutes), alpha 2-adrenergic activation with clonidine 150 micrograms i.v., insulin hypoglycaemia (0.15 U/kg soluble insulin), L-arginine infusion (30 g from 0 to 30 minutes), L-dopa (500 mg orally) and oral glucose (100 g). Groups of healthy male volunteers aged 20-42 years, all within 10% of ideal body weight. Serum GH and plasma GHRH 1-44 NH2 and 1-40 OH were measured at intervals for between 60 and 390 minutes, depending on the stimulation test. There were no significant changes in either GHRH 1-44 or 1-40 following alpha-adrenergic activation with propranolol/adrenaline infusion, alpha 2-adrenergic activation with i.v. clonidine, insulin-induced hypoglycaemia or arginine infusion despite the expected rise in GH levels. After oral glucose, GH was initially suppressed with a late rise. There were no changes in GHRH 1-44 or 1-40 levels during either phase of this response. After L-dopa GH levels peaked at 90 minutes, 24.5 +/- 11.0 mU/l (mean +/- SEM). At 0 minutes GHRH 1-44 and 1-40 levels were 3.25 +/- 0.89 and 4.93 +/- 1.28 pmol/l respectively and rose in both cases, peaking at 60 minutes at 4.23 +/- 1.01 and 7.55 +/- 1.80 pmol/l (P < 0.05). At no time was there any evidence of differential secretion of GHRH 1-44 or 1-40. We have confirmed previous studies demonstrating a small rise in GHRH before the GH response to L-dopa. However, in all other situations of pharmacological stimulation of GH release we were unable to detect any significant changes in GHRH 1-44 or 1-40 levels. It seems most likely that peripheral GHRH does not reflect hypothalamic secretion. As yet there is no evidence for differential release of GHRH 1-44 and 1-40.