Pyridostigmine Blocks the Inhibitory Effect of Glucocorticoids on Growth Hormone-Releasing Hormone Stimulated Growth Hormone Secretion in Normal Man

Abstract

Glucocorticoids have been shown to inhibit GH secretion in normal man when acutely and chronically administered in pharmacological amounts. Pyridostigmine (PD), an acetylcholinesterase inhibitor, is able to elicit GH secretion when administered alone and to enhance the GH response to GHRH in normal subjects probably via a decrease in the hypothalamic release of somatostatin. The aim of the present study was to investigate the influence of glucocorticoids on the GH response to PD administered either alone or in combination with GHRH in normal adult subjects. Six healthy adult volunteers underwent six experimental protocols. They received 1) human (h) GHRH(1-29)NH2, 100 micrograms injected as an iv bolus; 2) cortisone acetate, 50 mg administered orally (po) 60 min before an hGHRH iv bolus injection; 3) PD, 120 mg administered po, 60 min before an hGHRH iv bolus injection; 4) PD and cortisone acetate, administered po 60 min before an hGHRH iv bolus injection; 5) PD, administered po 60 min before a saline iv bolus injection; 6) PD and cortisone acetate administered po 60 min before a saline iv bolus injection. Mean GH levels, peak GH levels, and GH area under the curves (AUCs) were significantly lower after GHRH + cortisone as compared to GHRH alone. However, these parameters were not significantly different after PD + GHRH + cortisone when compared to PD + GHRH and after PD + cortisone when compared to PD alone. We conclude that acute administration of pharmacological amounts of glucocorticoids cannot inhibit the GH response to PD alone or in combination with GHRH. Thus, we hypothesize that the inhibitory action of glucocorticoids on the GH response to GHRH in man may be mediated by an enhancement of either somatostatin release by the hypothalamus or somatostatin action on the pituitary.

Hypothalamic Regulation of Impaired Growth Hormone Secretion in Diabetic Rats

“…Indeed, SRIF-Ab has been shown to significantly alter the GH response to GHRH in spontaneously diabetic rats [26]. PD has previously been used to alter GH secretion in hu mans [5,19,20,27], Dose-response studies in rats using PD over the range of 10-1.000 pg/kg have demonstrated 503 that even the lowest dose was effective in increasing GH concentrations [unpubl. observations].…”

Mechanisms of Steroid Impairment of Growth

“…At the hypothalamus, GC excess enhances somatostatin release or action [4]. When subjected to a long-term high-dose exposure to a GC, the pituitary somatotroph has a diminished response to GHRH [5, 6].…”

Hypothalamic Regulation of Impaired Growth Hormone Secretion in Diabetic Rats

“…SRIF is known to be present in the D-cell of the pancreatic islets and throughout the gastrointestinal tract in mucosal cells and in the enteric plexus [23,24], In view of the fact that in the spontaneously diabetic BB/Wor rats there is a marked re duction of islet D-cell mass with a concomitant reduction in D-cell secretory reserve [25,26] the pancreas may not be the source of hypersomatostatinemia in these animals. Other gastrointestinal sources, in particular the stomach, have been suggested as the probable site of SRIF over production.…”