Borkowski A J, Levin S, Delcroix C, Mahler A, Verhas V
J Clin Invest. 1967 May;46(5):797-811. doi: 10.1172/JCI105580.
A kinetic study of the conversion of blood cholesterol into hydrocortisone was carried out in two patients through prolonged infusions of cholesterol-4-(14)C. The following points appear to be established by our observations:1) The infused tracer behaved metabolically like endogenous cholesterol; it could therefore serve as a means of labeling plasma cholesterol for investigating its utilization by the adrenal cortex.2) At rest, about 80% of hydrocortisone derived from plasma cholesterol, the other 20% thus being synthesized in situ from acetate and other unlabeled precursors.3) Under ACTH stimulation the participation of plasma cholesterol in the synthesis of hydrocortisone was the same as at rest; the conversion of plasma cholesterol into hydrocortisone was thus proportional to the production of glucocorticosteroids by the adrenal glands.4) The specific activities of hydrocortisone allowed us to trace its adrenal precursors including adrenal cholesterol. The kinetics of the replacement of adrenal cholesterol by plasma cholesterol underlined the functional heterogeneity of the former. The experimental data were compatible with the following model: A fraction of plasma cholesterol entering the adrenal cell is immediately available for metabolism and conversion into steroid hormones, and another fraction turns over slowly, representing some form of storage.
通过对两名患者长时间输注胆固醇-4-(14)C，开展了血液胆固醇转化为氢化可的松的动力学研究。我们的观察结果似乎确立了以下几点：1）注入的示踪剂在代谢方面与内源性胆固醇相似；因此，它可作为标记血浆胆固醇的一种手段，用于研究肾上腺皮质对其的利用情况。2）在静息状态下，约80%的氢化可的松源自血浆胆固醇，另外20%则由醋酸盐和其他未标记的前体物质在原位合成。3）在促肾上腺皮质激素（ACTH）刺激下，血浆胆固醇在氢化可的松合成中的参与情况与静息时相同；因此，血浆胆固醇向氢化可的松的转化与肾上腺糖皮质激素的产生成正比。4）氢化可的松的比活性使我们能够追踪其肾上腺前体，包括肾上腺胆固醇。血浆胆固醇替代肾上腺胆固醇的动力学突出了肾上腺胆固醇的功能异质性。实验数据与以下模型相符：进入肾上腺细胞的一部分血浆胆固醇可立即用于代谢并转化为甾体激素，另一部分周转缓慢，代表某种形式的储存。
