Effects of recombinant human insulin-like growth factor I administration on the growth hormone (GH) response to OH-releasing hormone in obesity

Circulating GH levels are reduced in obesity due to true reduction of the 2 4-h GH production rate. GH insufficiency in obesity might reflect neuroendo crine abnormalities and/or alterations in peripheral hormones and metabolic factors. The somatotroph response to provocative stimuli including GHRH is markedly blunted in obese patients. However, the somatotroph responsivenes s to GHRH in obesity shows also peculiar refractoriness to the inhibitory e ffect of glucose load. In this present study we aimed at verifying the effe ct of low dose rhIGF-I (20 mug/kg, sc, at 0 min) on the GH response to GHRH (1 mug/kg, iv, at 180 min) in obesity. With this goal in mind, six obese w omen with abdominal adiposity [OB; age (mean +/- SEM), 32.3 +/- 4.4 yr; bod y mass index, 32.8 +/- 2.3 kg/m(2)] were studied. The effects of recombinan t human insulin-like growth factor I (rhIGF-I) administration on circulatin g total IGF-I, insulin, and glucose levels were also evaluated. The results in OB were compared with those recorded in age-matched lean women (NW; age , 28.3 +/- 1.2 yr; body mass index, 20.1 +/- 0.5 kg/m2), in whom the inhibi tory effect of rhIGF-I had already been shown. Basal IGF-I levels in OB wer e similar to those in NW (199.7 +/- 33.3 vs. 274.4 +/- 25.3 mug/L). The mea n GH concentration over 3 h (from 0-180 min) in OB was lower than that in N W (0.9 +/- 0.4 vs. 2.6 +/- 0.8 mug/L; P = NS). Administration of GHRH induc ed a GH response in OB lower than that in NW (area under the curve from 180 -270 min, 576.5 +/- 137.5 vs. 1315.9 +/- 189.9 mug/L min; P < 0.02). Admini stration of rhIGF-I increased circulating IGF-I levels in both groups to th e same percent extent (326.8 +/- 28.3 and 420.3 +/- 26.5 <mu>g/L in OB and NW, respectively), rhIGF-I administration inhibited the GH response to GHRH in OB (240.1 +/- 99.6 mug/L; P < 0.05) as well as in NW (730.2 +/- 288.1 < mu>g/L; P < 0.05), although it failed to lower the mean GH concentration ov er 3 h in either OB or NW. After rhIGF-I the GH response to GHRH in OB was slight and was still lower (P < 0.05) than that in NW; in fact, the percent decreases were similar in both groups (44.21 +/- 14.06 and 48.21 +/- 13.95 mug/L, in OB and NW, respectively). The mean insulin (107.1 +/- 21.9 and 3 6.8 +/- 7.2 pmol/L), but not glucose (4.0 +/- 0.3 and 4.1 +/- 0.1 mmol/L), levels calculated over 270 min, were higher (P = 0.005) in OB than in NW; r hIGF-I administration did not modify insulin and glucose levels in either g roup. Our study shows that the sc administration of a low rhIGF-I dose inhi bits the somatotroph responsiveness to GHRH in obese as well as in normal s ubjects, indicating that somatotroph sensitivity to the inhibitory effect o f rhIGF-I is preserved in obesity.