INFLUENCE OF CHRONIC NALTREXONE TREATMENT ON GROWTH-HORMONE AND INSULIN-SECRETION IN OBESE SUBJECTS

OBJECTIVE: Recent studies have demonstrated the restoration of a norma l 24 h GH profile induced by a reduction of insulinaemia after weight loss, suggesting a reciprocal relationship between plasma insulin and GH concentrations. We aimed to clarify if an opiate-induced reduction in plasma insulin could affect GH secretion in obesity. DESIGN: We hav e studied the insulin response to an oral glucose tolerance test (OGTT ) and the GH response to GHRH before and after prolonged treatment wit h Naltrexone (NTX). C-peptide, IGF-I, IGFBP-3 plasma levels and the IG F-I/ IGFBP-3 molar ratio were also determined. SUBJECTS: Twelve obese women (aged 25-41 y; Body mass index (BMI): 31-39 kg/m(2)) and six lea n normal women (aged 25-38; BMI: 19.8-23.1 kg/m(2)). MEASUREMENT: GH w as determined by the IRMA method; insulin, C-peptide, IGF-I and IGFBP9 were assayed by the RIA method. For molar comparison between IGF-I an d IGFBP-3 we have considered 30.5 kDa the molar weight of IGFBP-3. Res ults are expressed as mean +/- s.e.m. RESULTS: We observed a significa nt decrease in basal concentration of both insulin (230.1 +/- 34.9 vs 133.2 +/- 16.9 pmol/ L; P < 0.005) and C-peptide (3.7 +/- 0.3 vs 2.4 /- 0.1 mu g/L; P < 0.02). No modifications in the insulin secretory re sponse to the OGTT were observed. A significant increase of the GHRH-i nduced GH peak response (7.7 +/- 1.4 vs 19.7 +/- 3.1 mu g/L; P < 0.01) and GH-AUC (533 +/- 151 vs 1415 +/- 339 mu g/L/120 min; P < 0.01) was found after NTX treatment. A negative correlation was found between b asal insulin and GH peak values, both before (r = -0.641, P = 0.027) a nd after NTX (r = -0.714, P = 0.013). No modifications were found in I GF-I, IGFBP-3 and IGF-I/IGFBP-3 molar ratio. Moreover, NTX affected ne ither the insulin response to OGTT or IGF-I, IGFBP-3 and IGF-I/IGFBP-3 molar ratio in a group of six lean controls. Conversely, NIX signific antly reduced the GH response to GHRH, when expressed as both peak and AUC values. CONCLUSIONS: The opiate antagonist significantly reduced basal insulin concentrations and augmented the GH response to GHRH in obese subjects. In the absence of modifications in IGF-I and IGFBP-3 p lasma levels and their molar ratio, we propose that insulin may exert a negative feedback on GH secretion.