BINDING OF ESTRADIOL-17 FATTY ACID-ESTERS TO PLASMA-PROTEINS
BINDING OF ESTRADIOL-17 FATTY ACID-ESTERS TO PLASMA-PROTEINS
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DOI：
10.1210/endo-121-2-738
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发表时间：
1987-08-01
期刊：
影响因子：
4.8
通讯作者：
HOCHBERG, RB
中科院分区：
文献类型：
--
作者：
LARNER, JM;ROSNER, W;HOCHBERG, RB
雌二醇的C-17脂肪酸酯是血液中循环的长效雌激素的独特家族。这些酯的雌激素作用的不寻常的持续时间以前已被证明与它们非常缓慢的代谢速率有关。然而，与其缓慢的代谢速率形成鲜明对比的是，这些酯从血液中的清除相对较快，与雌二醇（E2）的清除没有很大差异。关于羧酸部分的大小对代谢和清除率的影响的研究表明，这些循环酯的细胞摄取可能涉及一个积极的过程，这反过来又提出了E2-脂肪酸酯如何在血液中转运的问题。研究了代表性E2-17-脂肪酸酯与已知结合E2或脂肪酸的人和大鼠血浆蛋白的结合。正如预期的那样，E2和5.alpha。双氢睾酮与人性激素结合球蛋白结合，而E2酯均不与该人血浆蛋白结合。类似地，E2结合到大鼠α-甲胎蛋白（AFP）和不饱和脂肪酸结合的人和大鼠AFP，但没有E2酯结合的AFP的任何物种。这些类固醇酯与脂蛋白结合。超过85%的代表性酯E2-17-硬脂酸酯分配在人和大鼠血清的脂蛋白级分中，而合成的短链酯E2- 17 β-硬脂酸酯分配在人和大鼠血清的脂蛋白级分中。醋酸，像E2本身，主要分配在血液的非脂蛋白部分。这些结果表明，不寻常的结合的类固醇激素家族的血浆脂蛋白和开放的可能性，它们被运送到靶细胞通过介导的脂蛋白受体。
The C-17 fatty acid esters of estradiol are a unique family of long-acting estrogens that circulate in blood. The unusual duration of the estrogenic action of these esters has been shown previously to correlate with their very slow rate of metabolism. However, in striking contrast to their slow rate of metabolism, the clearance of these esters from blood is relatively rapid, not very different from that of estradiol (E2). Studies on the effect of the size of the carboxylic acid moiety on the rates of both metabolism and clearance have suggsted that an active process might be involved in the cellular uptake of these circulating esters, and this, in turn, raised the question of how E2-fatty acid esters are transported in blood. The binding of representative E2-17-fatty acid esters to both human and rat plasma proteins known to bind either E2 or fatty acids was investigated. As expected, both E2 and 5.alpha.-dihydrotestosterone bound to human sex hormone-binding globulin, whereas none of the E2 esters bound to this human plasma protein. Similarly, E2 bound to rat .alpha.-fetoprotein (AFP) and unsaturated fatty acids bound to both human and rat AFP, but none of the E2 esters bound to AFP of either species. These steroid esters bind to lipoproteins. Over 85% of a representative ester, E2-17-stearate, partitioned in the lipoprotein fractions of both human and rat serum, while the synthetic short chain ester, E2-17.beta.-acetate, like E2 itself, partitioned predominantly in the nonlipoprotein fraction of blood. These results demonstrate the unusual binding of a family of steroid hormones to plasma lipoproteins and open the possibility that they are transported into target cells through the mediation of lipoprotein receptors.