Pardridge W M, Sakiyama R, Judd H L
J Clin Endocrinol Metab. 1983 Jul;57(1):160-5. doi: 10.1210/jcem-57-1-160.
It is generally regarded that only free corticosteroid is available for entry into tissues in vivo, although some studies have suggested that albumin-bound corticosteroid is available for liver uptake. However, recent studies suggest that owing to favorable kinetic relationships among tissue capillary transit times and hormone dissociation rates from plasma proteins, free plus albumin-bound hormone may be available to peripheral tissues. Moreover, globulin-bound hormone may enter the liver under normal conditions and be available to peripheral tissues under pathological circumstances. The present studies measure the free and noncorticosteroid-binding globulin (non-CBG)-bound corticosteroid fractions in vitro and compare these measurements to the fraction of corticosteroid in human sera that is available for entry into rat brain and rat liver in vivo. Corticosterone was used as the model corticosteroid, since this compound binds to CBG with the same affinity as does cortisol, and the brain extraction of corticosterone is more readily measured in vivo than is the brain extraction of cortisol. Serum was obtained from 51 human subjects and included samples from newborns, pregnant mothers, normal subjects, and patients with either cirrhosis or renal failure. Serum levels of CBG varied more than 6-fold, and both the free and the non-CBG-bound fractions were generally inversely related to the CBG concentration. The fraction of corticosterone available for entry into the brain was much greater than the free fraction, but was not significantly different from the non-CBG-bound moiety. Moreover, the rate of corticosterone dissociation from CBG (t 1/2 = 27 +/- 1 sec at 22 C) was not increased in any of the serum samples studied. The fraction of corticosterone available for uptake by the liver was up to 3-fold greater than that of the non-CBG fraction and had no relationship with the serum concentration of CBG. These studies indicate that albumin-bound, but not globulin-bound, corticosteroid is available for entry into a peripheral tissue such as the brain. However, globulin-bound corticosteroid is readily transported into the liver. It is suggested that the routine measurements of the non-CBG-bound corticosteroid provide a more accurate index of the corticosteroid available to peripheral tissues in vivo than does the measurement of free corticosteroid.
一般认为，在体内只有游离皮质类固醇能够进入组织，尽管一些研究表明，与白蛋白结合的皮质类固醇可被肝脏摄取。然而，最近的研究表明，由于组织毛细血管通过时间与激素从血浆蛋白解离速率之间存在有利的动力学关系，游离的以及与白蛋白结合的激素可能会被外周组织利用。此外，与球蛋白结合的激素在正常情况下可能进入肝脏，并在病理情况下被外周组织利用。本研究在体外测量游离的以及与非皮质类固醇结合球蛋白（非CBG）结合的皮质类固醇部分，并将这些测量结果与人体血清中可进入大鼠脑和大鼠肝脏的皮质类固醇部分进行比较。使用皮质酮作为模型皮质类固醇，因为该化合物与CBG的结合亲和力与皮质醇相同，并且与皮质醇相比，皮质酮在体内的脑摄取更容易测量。从51名人类受试者获得血清，包括新生儿、孕妇、正常受试者以及肝硬化或肾衰竭患者的样本。血清中CBG水平变化超过6倍，游离部分和非CBG结合部分通常与CBG浓度呈负相关。可进入脑的皮质酮部分远大于游离部分，但与非CBG结合部分无显著差异。此外，在所研究的任何血清样本中，皮质酮从CBG的解离速率（22℃时t1/2 = 27±1秒）均未增加。可被肝脏摄取的皮质酮部分比非CBG部分高3倍，且与血清CBG浓度无关。这些研究表明，与白蛋白结合而非与球蛋白结合的皮质类固醇可进入外周组织如脑。然而，与球蛋白结合的皮质类固醇很容易转运到肝脏。有人提出，常规测量非CBG结合的皮质类固醇比测量游离皮质类固醇能提供更准确的体内可被外周组织利用的皮质类固醇指标。
