Gianotti L, Ramunni J, Lanfranco F, Maccagno B, Giordano R, Broglio F, Maccario M, Muller E E, Ghigo E, Arvat E
Department of Internal Medicine, University of Turin, Italy.
J Endocrinol Invest. 2001 Feb;24(2):67-71. doi: 10.1007/BF03343815.
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.
有人提出胰岛素样生长因子-I（IGF-I）对下丘脑-垂体-肾上腺（HPA）轴具有抑制作用。事实上，已有报道称重组人生长激素（rhGH）诱导的IGF-I增加会抑制动物体内皮质醇和生长激素对MK-0677（一种非肽类生长激素促分泌素）的反应。本研究的目的是进一步阐明IGF-I对促肾上腺皮质激素细胞功能是否具有抑制作用（若有）。我们研究了重组人IGF-I（rhIGF-I；-180分钟时皮下注射20μg/kg）或安慰剂对正常年轻女性促肾上腺皮质激素（ACTH）和皮质醇对人促肾上腺皮质激素释放激素（hCRH；0分钟时静脉注射2.0μg/kg）或六肽生长激素释放肽（HEX；0分钟时静脉注射2.0μg/kg，一种肽类生长激素促分泌素）反应的影响。还研究了rhIGF-I对生长激素对HEX反应的影响。研究对象为6名处于卵泡早期的正常年轻女性[年龄：26 - 35岁；体重指数（BMI）：19 - 23kg/m²]。结果显示，皮下注射rhIGF-I后，循环中的IGF-I水平升高约77%，在-60分钟时达到峰值，并持续至+120分钟左右保持相似水平。在给予安慰剂或rhIGF-I后评估，从-180分钟至0分钟，平均ACTH、皮质醇和生长激素浓度均未改变。CRH和HEX诱导出相似的ACTH反应（峰值与基线相比，平均±标准误：分别为47.5±10.9对21.3±3.0pg/ml和30.3±6.9对19.2±3.8pg/ml，p<0.04）和皮质醇反应（分别为177.5±5.4对109.3±10.3μg/l和149.4±12.3对119.8±16.4μg/l，p<0.04）。rhIGF-I预处理并未改变ACTH和皮质醇对hCRH的反应（分别为46.0±13.8pg/ml和181.1±16.9μg/l）以及对HEX的反应（分别为28.8±5.0pg/ml和144.1±16.2μg/l）。另一方面，rhIGF-I明显降低了生长激素对HEX的反应（23.9±4.7对64.7±14.8μg/l，p<0.05）。我们的研究结果表明，rhIGF-I诱导的循环IGF-I水平升高对生长激素分泌细胞分泌发挥负反馈作用，而对促肾上腺皮质激素细胞和肾上腺对CRH或六肽生长激素释放肽的反应无影响。
