ACTIVATION OF CHOLINERGIC TONE BY PYRIDOSTIGMINE REVERSES THE INHIBITORY EFFECT OF CORTICOTROPIN-RELEASING HORMONE ON THE GROWTH HORMONE-RELEASING HORMONE-INDUCED GROWTH-HORMONE SECRETION

Previous studies have shown that corticotropin-releasing hormone (CRH) is capable of inhibiting growth hormone (GH) secretion in response to GH-releasing hormone (GHRH). In an attempt to clarify the mechanism of the CRH action, we have studied the effect of enhanced cholinergic tone induced by pyridostigmine on the CRH inhibition of the GH response to GHRH in a group of six normal men and six normal women. All subjects presented a normal GH response to 50-mu-g iv GHRH administration (mean peak +/- SEM plasma GH levels 20 +/- 2.9-mu-g/l in men and 28.9 +/- 2.9-mu-g/l in women) with a further significant increase after pyridostigmine pretreatment (60 mg orally given 60 min before GHRH) in men (GH peaks 4 3.1 +/- 6.9-mu-g/l, p < 0.00 5) but not in women (GH peaks 39.2 +/- 3.0-mu-g/l). In the same subjects, peripherally injected CRH (100-mu-g) significantly inhibited the GH response to GHRH (GH peaks 8.1 +/- 0.6-mu-g/l in men, p < 0.005 and 9.9 +/- 0.7-mu-g/l in women, p < 0.005). Pyridostigmine (60 mg) given orally at the same time of CRH administration (60 min before GHRH) reversed the CRH inhibition of GHRH-induced GH secretion (GH peaks 35.3 +/- 8.2-mu-g/l in men and 35 +/- 3.3-mu-g/l in women) with a response not significantly different to that seen in the pyridostigmine plus GHRH test. Our data confirm that pyridostigmine is capable of potentiating the GHRH-induced GH release in normal male but not female subjects. In addition, our studies show that the potentiating action of pyridostigmine on the GHRH-induced GH secretion prevails on the inhibiting effect of CRH when the two drugs are given together 1 h before GHRH injection. Both CRH and pyridostigmine could exert their action by modifying, in opposite ways, somatostatin release from the hypothalamus.