Recombinant human IGF-I does not modify the ACTH and cortisol responses to hCRH and hexarelin, a peptidyl GH secretagogue, in humans

An inhibitory influence of insulin-like growth factor-I (IGF-I) on hypothalamus-pituitary-adrenal (HPA) axis has been hypothesized. In fact, it has been reported that the rhGH (recombinant human GH)-induced IGF-I increase inhibits both cortisol and GH response to MK-0677, a non-peptidyl GH secretagogue in animals. The aim of this study was to further clarify the inhibitory role, if any, of IGF-I on corticotroph function. We studied the effect of rhIGF-I (recombinant human IGF-I; 20 μg/kg sc at −180 min) or placebo on the ACTH and cortisol responses to hCRH (human CRH; 2.0 μg/kg iv at 0 min) or hexarelin (HEX; 2.0 μg/kg iv at 0 min), a peptidyl GHS, in normal young women. The effect of rhIGF-I on the GH response to HEX was also studied. The subjects were six normal young women [age: 26–35 yr; body mass index (BMI): 19–23 kg/m2] in their early follicular phase. The results showed that after sc rhIGF-I administration, circulating IGF-I levels increased approximately 77%, peaking at −60 min and persisting similar up to +120 min. The mean ACTH, cortisol and GH concentrations did not change from −180 to 0 min when evaluated after both placebo or rhIGF-I. CRH and HEX induced similar ACTH (peak vsbaseline, mean±SE: 47.5±10.9 vs 21.3±3.0 pg/ml and 30.3±6.9 vs 19.2±3.8 pg/ml, respectively; p<0.04) and cortisol responses (177.5±5.4 vs109.3±10.3 μg/l and 149.4±12.3 vs 119.8±16.4 μg/l, respectively, p<0.04). RhIGF-I pre-treatment did not modify the ACTH and cortisol responses to hCRH (46.0±13.8 pg/ml and 181.1±16.9 μg/l, respectively) as well as those to HEX (28.8±5.0 pg/ml and 144.1±16.2 μg/l, respectively). On the other hand, the GH response to HEX was clearly reduced by rhIGF-I (23.9±4.7 vs64.7±14.8 μg/l, p<0.05). Our findings show that rhIGF-I-induced increase of circulating IGF-I levels exerts negative feedback action on somatotroph secretion, while it does not modify the corticotroph and the adrenal responsiveness to CRH or hexarelin.