Chrousos G P, Calabrese J R, Avgerinos P, Kling M A, Rubinow D, Oldfield E H, Schuermeyer T, Kellner C H, Cutler G B, Loriaux D L
Prog Neuropsychopharmacol Biol Psychiatry. 1985;9(4):349-59. doi: 10.1016/0278-5846(85)90187-3.
Corticotropin releasing factor (CRF) is a newly sequenced peptide first isolated from sheep hypothalami and thought to be an important modulator of both the pituitary-adrenal axis and the sympathetic nervous system. We administered intravenous, intramuscular, and intracerebroventricular CRH to non-human primates and measured plasma ACTH, beta endorphin, cortisol, GH and PRL responses to CRF. In addition, we determined the pharmacokinetic properties of I125 in these primates. We administered CRF as an intravenous bolus or as a continuous infusion to normal volunteers and as an intravenous bolus to patients with disorders of the hypothalamic-pituitary-adrenal axis, such as Cushing's syndrome and adrenal insufficiency, and patients with endogenous depression and mild hypercortisolism, and assessed their plasma ACTH, cortisol, GH and PRL responses. In addition, we determined the pharmacokinetic properties of CRF in man by measuring CRF immunoreactivity in plasma. CRF given intravenously to primates or man is a slowly metabolized, long-acting, secretagogue of ACTH, beta-endorphin and cortisol. When given intracerebroventricularly to primates it stimulates the hypothalamic-pituitary-adrenal axis without escaping into the plasma and it is actively cleared in the CNS. It does not cross the blood brain barrier appreciably when given intravenously. CRF given to primates and men as an intravenous continuous infusion has only mild ACTH stimulating effects and this may be due to an intact cortisol negative feedback system. Finally, CRF causes characteristic plasma hormone responses in patients with Cushing's disease, adrenal insufficiency and depression.
促肾上腺皮质激素释放因子（CRF）是一种新测序的肽，最初从绵羊下丘脑分离出来，被认为是垂体 - 肾上腺轴和交感神经系统的重要调节因子。我们给非人类灵长类动物静脉内、肌肉内和脑室内注射促肾上腺皮质激素释放激素（CRH），并测量血浆促肾上腺皮质激素（ACTH）、β-内啡肽、皮质醇、生长激素（GH）和催乳素（PRL）对CRF的反应。此外，我们还测定了这些灵长类动物中碘-125的药代动力学特性。我们给正常志愿者静脉推注或持续输注CRF，给患有下丘脑 - 垂体 - 肾上腺轴疾病（如库欣综合征和肾上腺功能不全）以及内源性抑郁症和轻度皮质醇增多症的患者静脉推注CRF，并评估他们的血浆ACTH、皮质醇、GH和PRL反应。此外，我们通过测量血浆中的CRF免疫反应性来确定CRF在人体内的药代动力学特性。静脉注射给灵长类动物或人的CRF是一种代谢缓慢、长效的ACTH、β-内啡肽和皮质醇促分泌素。当给灵长类动物脑室内注射时，它刺激下丘脑 - 垂体 - 肾上腺轴而不会逸入血浆，并且在中枢神经系统中被积极清除。静脉注射时它不会明显穿过血脑屏障。给灵长类动物和人静脉持续输注CRF只有轻微的ACTH刺激作用，这可能是由于完整的皮质醇负反馈系统。最后，CRF在库欣病、肾上腺功能不全和抑郁症患者中引起特征性的血浆激素反应。
