EFFECT OF COMBINED ADMINISTRATION OF GROWTH-HORMONE (GH)-RELEASING HORMONE, GH-RELEASING PEPTIDE-6, AND PYRIDOSTIGMINE IN NORMAL AND OBESE SUBJECTS

Growth hormone (GH) secretion in response to all provocative stimuli i s decreased in patients with obesity. Recently, we found that the comb ined administration of GH-releasing hormone (GHRH) and the hexapeptide GH-releasing peptide-6 (GHRP-6) induced a large increase in plasma GH levels. To gain further insight into the disrupted mechanism of GH re gulation in obesity, we investigated whether the inhibition of somatos tatinergic tone with pyridostigmine could further increase the GH resp onse to combined administration of GHRH and GHRP-6. In normal subjects , administration of GHRH plus GHRP-6 induced a marked increase in plas ma GH with a peak at 30 minutes (mean +/- SEM, 76.7 +/- 9.7 mu g/L), w hich was similar to that obtained after pretreatment with pyridostigmi ne (74.7 +/- 9.4 mu g/L). In obese patients, combined administration o f GHRH plus GHRP-6 induced a clear increase in GH secretion with a pea k at 15 minutes of 42.2 +/- 10.0 mu g/L, which was also unaffected aft er pretreatment with pyridostigmine (38.4 +/- 5.8 mu g/L). The GH resp onse was lower in obese patients than in controls as assessed by the a rea under the curve after administration of both GHRH plus GHRP-6 (1,8 46 +/- 396 v 4,773 +/- 653, P < .01) and pyridostigmine plus GHRH plus GHRP-6 (1,989 +/- 372 v 5,098 +/- 679, P < .005). In conclusion, thes e data suggest that GHRP-6 can behave as a functional somatostatin ant agonist, and that somatotrope responsiveness to the combined administr ation of GHRH plus GHRP-6 is largely independent of somatostatinergic tone. Therefore, our findings in obese subjects of a relatively high G H response to GHRH plus GHRP-6, albeit low in comparison to that in no rmal subjects, with or without pyridostigmine suggest that the somatot rope cell in obesity has a considerable GH secretory capacity. Copyrig ht (C) 1995 by W.B. Saunders Company