Repeated GH-releasing hormone administration unravels different GH secretory patterns in normal adults and children

Abstract

Abstract. In normal adults, repeated GHRH administration leads to progressively decreasing somatotrope responses. To verify whether this GH secretory pattern also connotes normal growing children, we have studied the effects of two consecutive (every 120 min) 1 μg/kg iv GHRH boluses on GH release in normal adults (N = 7, age 23.2–30.6 years) children (N = 6, age 10.4–13.2 years). In the adults, the GH response to the second GHRH bolus (peak, mean ± sem: 2.9 ± 0.8 μg/l) was lower (P< 0.02) than that to the first bolus (15.9 ± 2.4 μg/l). Conversely, in children the GH response to the second GHRH bolus (25.6 ± 6.3 μg/l) overrode the first one (13.6 ± 6.5 μg/l), but this difference did not attain statistical significance. In adults cholinergic enhancement by pyridostigmine, a cholinesterase inhibitor, was previously shown to re-instate, even to potentiate somatotrope responsiveness to consecutive GHRH boluses. Thus, in 5 children GH response to repeated GHRH boluses was retested administering pyridostigmine (60 mg orally) 30 min before the second GHRH bolus. In these subjects, pyridostigmine failed significantly to potentiate the GH responsiveness to the second GHRH bolus (30.3 ± 4.6 vs 25.0 ± 7.6 μg/l). These data indicate that differently from in adults, in children repeated GHRH administration does not reduce somatotrope responsiveness and that cholinergic enhancement fails to potentiate GH responsiveness to the second GHRH bolus.

Growth hormone (GH) rebound rise following somatostatin infusion withdrawal: studies in dogs with the use of GH-releasing hormone and a GH-releasing peptide

“…The increase in plasma GH concentrations would enhance hypothalamic SS tone (and probably reduce concomitantly the activity of GHRH-secreting neurons) (43±47), thus blunting the subsequent responsiveness to GHRH. Supporting this proposition is the ®nding that a cholinergic drug, pyridostigmine, which inhibits SS release (48), given before the second GHRH bolus, reinstates GH responsiveness to the peptide in humans (49,50).…”

GH responses to two consecutive bouts of neuromuscular electrical stimulation in healthy adults

“…It is well established that repeated GHRH stimuli (2)(3)(4)(5) or voluntary exercise bouts (6-8, 15, 16) administered at 2-h intervals are associated with a blunted GH responsiveness to the second stimulus in healthy adults, a restoration of GH responsiveness being present when the time elapsed between the two stimuli was more prolonged (8,17).…”

“…It is well known that repeated GHRH stimuli administered at 2-h intervals are associated with a complete blunting of GH responsiveness to the second stimulus in healthy adults (2)(3)(4)(5), with a restoration of GH responsiveness occurring when the time elapsed between the two pharmacological stimuli was more prolonged.…”

GH responses to two consecutive bouts of whole body vibration, maximal voluntary contractions or vibration alternated with maximal voluntary contractions administered at 2-h intervals in healthy adults

“…Increased GH concentrations evoke prompt hypothalamic somatostatin release, which in turn inhibits GHRH secretion, blocks pituitary GH exocytosis GH and sensitizes somatotrophs to the next GHRH stimulus [1]. In healthy adults, repeated GHRH stimuli administered at 2-h intervals are associated with blunting of GH responsiveness to the second stimulus [2][3][4][5], with restoration of GH responsiveness occurring when the time elapsed between the two pharmacological stimuli is longer [6].…”