Studies on phenolic steroids in human subjects. II. The metabolic fate and hepato-biliary-enteric circulation of C14-estrone and C14-estradiol in women.
Studies on phenolic steroids in human subjects. II. The metabolic fate and hepato-biliary-enteric circulation of C14-estrone and C14-estradiol in women.
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对人体酚类类固醇的研究。
DOI：
10.1172/jci103524
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发表时间：
1957
期刊：
影响因子：
--
通讯作者：
W. Slaunwhite
中科院分区：
文献类型：
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作者：
A. Sandberg;W. Slaunwhite
多年来，人们已经知道，在受试者的尿液中，只有一小部分服用雌酮或雌二醇的代谢物可以被明确识别出来(1-6)。通过化学或生物分析，最多有10%到20%的注射雌激素在尿液中被回收。从1928年起，动物的胆汁和女性的粪便中就发现了雌激素的存在(7，8)，但直到坎塔罗、皮尔曼、帕施基斯、拉科夫、汉森和Walking的努力，狗的胆汁排泄才被证明是雌激素排泄的主要途径(9-13)。随后，这些研究人员在孕妇的胆汁中显示了大量的雌激素活性(14)。有趣的是，研究表明，动物胆汁中的雌激素以游离形式存在，而孕妇胆汁中存在结合类固醇(6，13)。基于他们广泛的实验，这些作者提出了雌激素参与肠-肝循环的理论。用放射性溴标记的雌酮和用IL31标记的雌二醇在胆汁中显著排泄。不幸的是，卤素的加入使雌激素在生物学上失去了活性，使研究结果很难与使用内源性类固醇获得的结果进行比较。此外，由于缺乏对所有雌激素代谢物的了解以及用于测定它们的方法的不完善，准确量化胆汁和尿液中的雌激素排泄量是不可能的。C‘4标记雌酮和雌二醇的出现使代谢研究成为可能。
It has been known for a number of years that only a small percentage of the metabolites of administered estrone or estradiol can be definitely identified in the urine of human subjects (1-6). At the most, 10 to 20 per cent of the injected estrogen were recovered in the urine either by chemical or biological assays. The presence of estrogens in bile of animals and in the feces of women had been known since 1928 (7, 8), but it was not until the efforts of Cantarow, Pearlman, Paschkis, Rakoff, Hansen and Walking that biliary excretion in the dog was shown to constitute a major route of excretion of estrogens (9-13). Subsequently, these investigators demonstrated substantial estrogenic activity in the bile of pregnant women (14). Interestingly, it was shown that the estrogens in the bile of animals existed in the free form, in contrast to the presence of conjugated steroids in the bile of pregnant women (6, 13). Based on their extensive experiments, these authors advanced the theory that estrogens participate in an enterohepatic circulation. Significant biliary excretion of estrone labelled with radioactive bromine and estradiol labelled with Il31 was demonstrated when these isotopes became available (15, 16). Unfortunately, the inclusion of the halogens renders the estrogens biologically inactive and makes the results of the studies difficult to compare with those obtained using endogenous steroids. Furthermore, precise quantification of biliary and urinary estrogen excretion was not possible due to lack of knowledge of all of the estrogen metabolites and imperfections of the methods used for their determination. The availability of C'4-labelled estrone and estradiol has made it possible to study the metabolic