Oelkers W, Buchen S, Diederich S, Krain J, Muhme S, Schöneshöfer M
Department of Endocrinology, Klinikum Steglitz, Freie Universität Berlin, Germany.
J Clin Endocrinol Metab. 1994 Apr;78(4):928-32. doi: 10.1210/jcem.78.4.8157723.
9 alpha-Fluorocortisol (9 alpha FF) is about 200 times more potent as a mineralocorticoid than cortisol (F) in man, although it binds with the same affinity as F and aldosterone to the human mineralocorticoid receptor. The low mineralocorticoid activity of F has been shown to be due to its rapid conversion by the kidney to cortisone (E), which does not bind to the receptor. Therefore, we compared the conversion of F to E with that of 9 alpha FF to 9 alpha-fluorocortisone (9 alpha FE) by 11-hydroxysteroid dehydrogenases in man in vivo and in vitro. Single oral doses of 9 alpha FF, 9 alpha FE, and F were given to normal males, and the excretion of free 9 alpha FF, 9 alpha FE, F, and E was measured in urine. Human kidney and liver slices were incubated with unlabeled steroids, and the free 11-hydroxy- and 11-oxosteroids were quantitated after high performance liquid chromatography separation by UV absorption. Oral F (5 mg) is excreted 70% as free E and 30% as free F (percentage of free steroids only). Oral 9 alpha FF (5 mg) is excreted 90% as free 9 alpha FF and 10% as free 9 alpha FE. Free 9 alpha FF excretion is 14 times greater than that of F after ingesting an identical dose. Oral 9 alpha FE (4 mg) is also excreted 90% as 9 alpha FF and 10% as 9 alpha FE. Kidney slices convert F much faster to E than 9 alpha FF to 9 alpha FE. The conversion of 9 alpha FE to 9 alpha FF is, on the contrary, much faster than that of E to F. Thus, the equilibrium of the reaction is on the 11-oxo side for F/E and on the 11-hydroxy side for 9 alpha FF/9 alpha FE. The interconversion of both pairs of steroids is inhibited by glycyrrhetinic acid in a dose-dependent manner. Liver slices do not measurably convert 9 alpha FF to 9 alpha FE, but do rapidly convert 9 alpha FE into 9 alpha FF. Reflecting this negligible conversion of 9 alpha FF to 9 alpha FE and the low plasma-protein binding of 9 alpha FF, free urinary 9 alpha FF excretion is much higher than that of F after the same oral dose.(ABSTRACT TRUNCATED AT 400 WORDS)
9α-氟皮质醇（9αFF）作为盐皮质激素，其效力在人体内比皮质醇（F）强约200倍，尽管它与F和醛固酮对人盐皮质激素受体的亲和力相同。已表明F的盐皮质激素活性低是由于其在肾脏中迅速转化为可的松（E），而E不与受体结合。因此，我们在体内和体外比较了人体内11-羟类固醇脱氢酶将F转化为E与将9αFF转化为9α-氟可的松（9αFE）的情况。给正常男性单次口服9αFF、9αFE和F，然后测定尿中游离9αFF、9αFE、F和E的排泄量。将人肾和肝切片与未标记的类固醇一起孵育，通过高效液相色谱分离后，利用紫外吸收对游离的11-羟基和11-氧代类固醇进行定量。口服F（5毫克）时，70%以游离E形式排泄，30%以游离F形式排泄（仅指游离类固醇的百分比）。口服9αFF（5毫克）时，90%以游离9αFF形式排泄，10%以游离9αFE形式排泄。摄入相同剂量后，游离9αFF的排泄量比F高14倍。口服9αFE（4毫克）时，同样90%以9αFF形式排泄，10%以9αFE形式排泄。肾切片将F转化为E的速度比将9αFF转化为9αFE的速度快得多。相反，9αFE转化为9αFF的速度比E转化为F的速度快得多。因此，对于F/E反应，平衡点在11-氧代侧；对于9αFF/9αFE反应，平衡点在11-羟基侧。这两对类固醇的相互转化均受到甘草次酸的剂量依赖性抑制。肝切片不能明显地将9αFF转化为9αFE，但能迅速将9αFE转化为9αFF。鉴于9αFF向9αFE的转化可忽略不计以及9αFF与血浆蛋白的结合率低，相同口服剂量后，尿中游离9αFF的排泄量远高于F。（摘要截选至400字）
