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 microg/kg s.c. at -180 min) or placebo on the ACTH and cortisol responses to hCRH (human CRH; 2.0 microg/kg i.v. at 0 min) or hexarelin (HEX; 2.0 microg/kg i.v. 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 s.c. 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 vs baseline, 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 vs 109.3+/-10.3 microg/l and 149.4+/-12.3 vs 119.8+/-16.4 microg/l, respectively, p<0.04). RhIGF-I pretreatment did not modify the ACTH and cortisol responses to hCRH (46.0+/-13.8 pg/ml and 181.1+/-16.9 microg/l, respectively) as well as those to HEX (28.8+/-5.0 pg/ml and 144.1+/-16.2 microg/l, respectively). On the other hand, the GH response to HEX was clearly reduced by rhIGF-I (23.9+/-4.7 vs 64.7+/-14.8 microg/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.
Gianotti
L
L
Department of Internal Medicine, University of Turin, Italy.
Ramunni
J
J
Lanfranco
F
F
Maccagno
B
B
Giordano
R
R
Broglio
F
F
Maccario
M
M
Muller
E E
EE
Ghigo
E
E
Arvat
E
E
D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000328:Adult; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D005246:Feedback; D005260:Female; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007700:Kinetics; D009842:Oligopeptides / Q000494:pharmacology*; D010919:Placebos; D011994:Recombinant Proteins / Q000494:pharmacology
D009842:Oligopeptides; D010919:Placebos; D011994:Recombinant Proteins; C086184:hexarelin; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D006854:Hydrocortisone