Continuous administration of synthetic ovine corticotropin-releasing factor in man. Physiological and pathophysiological implications.
Continuous administration of synthetic ovine corticotropin-releasing factor in man. Physiological and pathophysiological implications.
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DOI：
10.1172/jci111890
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发表时间：
1985-06
期刊：
影响因子：
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通讯作者：
H. Schulte;G. Chrousos;P. Gold;J. Booth;E. Oldfield;G. Cutler;D. Loriaux
中科院分区：
文献类型：
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作者：
H. Schulte;G. Chrousos;P. Gold;J. Booth;E. Oldfield;G. Cutler;D. Loriaux
连续24小时输注最大刺激剂量绵羊促肾上腺皮质激素释放因子（CRF）（1微克/千克/小时）在人引起血浆皮质醇适度升高（17.2 +/- 1.4微克/分升）和尿游离皮质醇（173 +/- 43微克/24小时）浓度，远低于最大刺激剂量的ACTH所观察到的浓度（分别为50.4 +/- 2.2微克/分升和1，200 +/- 94微克/24小时）。CRF给药期间，血浆ACTH和皮质醇的昼夜节律得以保持。在基础条件下，对正常志愿者静脉推注1 μ g/kg绵羊CRF导致血浆ACTH和皮质醇峰值水平升高（分别为28 +/- 6 pg/ml和15.0 +/- 1.0 μ g/dl）。然而，当在连续输注结束时进行相同的CRF刺激试验时，未观察到血浆ACTH和皮质醇反应。这些结果表明，外源性CRF对垂体ACTH分泌细胞的刺激活性受到皮质醇负反馈的抑制。持续的昼夜节律的促肾上腺皮质激素，尽管在输液过程中的血浆CRF的水平恒定，表明昼夜变化的活动下丘脑-垂体-肾上腺轴不能被解释的内源性CRF刺激的昼夜周期性。
The continuous 24-h infusion of a maximally stimulating dose (1 micrograms/kg per h) of ovine corticotropin-releasing factor (CRF) in man caused a modest elevation of plasma cortisol (17.2 +/- 1.4 micrograms/dl) and urinary-free cortisol (173 +/- 43 micrograms/24 h) concentrations, which was far less than that seen with a maximally stimulating dose of ACTH (50.4 +/- 2.2 micrograms/dl and 1,200 +/- 94 micrograms/24 h, respectively). The circadian rhythms of plasma ACTH and cortisol were preserved during CRF administration. An intravenous bolus injection of 1 microgram/kg of ovine CRF given to normal volunteers under basal conditions resulted in elevated plasma ACTH and cortisol peak levels (28 +/- 6 pg/ml and 15.0 +/- 1.0 micrograms/dl, respectively). However, no plasma ACTH and cortisol responses were observed when an identical CRF stimulation test was given at the end of the continuous infusion. These findings suggest that the stimulatory activity of exogenous CRF on the ACTH-secreting cells of the pituitary gland is restrained by the negative feedback of cortisol. The persistent circadian rhythm of ACTH, despite a constant level of plasma CRF during the infusion, suggests that the circadian variation in the activity of the hypothalamic-pituitary-adrenal axis cannot be explained solely by circadian periodicity of the endogenous CRF stimulus.