QUANTITATIVE STUDIES ON THE METABOLISM OF DEHYDROISOANDROSTERONE SULFATE.
QUANTITATIVE STUDIES ON THE METABOLISM OF DEHYDROISOANDROSTERONE SULFATE.
复制标题
硫酸脱氢异雄酮代谢的定量研究。
DOI：
10.1021/bi00897a013
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发表时间：
1964
期刊：
影响因子：
2.9
通讯作者：
S. Lieberman
中科院分区：
文献类型：
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作者：
E. Sandberg;E. Gurpide;S. Lieberman
将~ 3 H-和~（35）S-标记的脱氢异雄酮硫酸盐（DS）和~（14）C-标记的脱氢异雄酮（D）的混合物注射到正常女性体内。注射后，在不同时间间隔采集血样2天，并测定血浆样品中DS中的3 H、35 S和14 C浓度。还测定了血浆中未标记DS的浓度。本文在双库（D和DS）模型的基础上，利用前文提出的方程，估算了DS的分布容积、血浆中DS的代谢清除率、血浆DS的产生率、DS向D的转化率、DS向其它产物的排泄和转化率。注射后3天收集尿液，测定从尿液中分离的DS和脱氢异雄酮葡糖苷酸（DG）的比活性。从这些具体活动的分泌和代谢率的DS和D的估计。在可能进行比较的情况下，发现从血浆数据中获得的DS代谢相关参数值与从尿液数据中获得的参数值无显著差异。在另一个实验中，将相同的示踪剂混合物注射到正常男性体内，并在注射后2小时内以短时间间隔采集血样。在这种情况下，检测到血浆中存在与DS交换的另一个硫酸盐池。讨论了它对解释女性受试者结果的影响。最近的几项发现表明，硫酸脱氢异雄酮（DS）1可能比单纯的尿代谢产物具有更大的生理重要性。例如，DS，血浆中最丰富的类固醇，已经显示在体内由肾上腺组织产生（Baulieu，1962; VandeWiele等人，1963）和在体外条件下（Wallace和Lieber-man，1963; Cohn等，1963; Migeon，1963）。事实上，就目前所知，肾上腺分泌DS是唯一的，因为没有其他内分泌腺的产物以结合形式分泌。另一个特征是DS和游离脱氢异雄酮（D）在正常情况下可相互转化（Roberts et al.，1961年）。已证明人胎盘组织（Warren和Timberlake，1962）可将DS转化为D，更令人惊讶的是，Siiteri和MacDonald（1963）以及Baulieu和Dray（1963）的研究表明，在孕妇中，循环DS可有效转化为雌激素。此外，类固醇硫酸盐可能具有排泄功能以外的功能的暗示从卡尔文的工作中得到了额外的支持（卡尔文等人，1963年;卡尔文和利伯曼，1964年），他们已经表明，这种共轭物经历的生物合成反应类似于通常被认为是激素的类固醇形成中所涉及的反应。这些事实强调了获得有关此类缀合物（特别是DS）的额外定量信息的不可行性。
A mixture of 3H-and 35S-labeled tracers of dehydroisoandrosterone sulfate (DS) and 14C-labeled dehydroisoandrosterone (D) was injected into a normal woman. Following the injection, samples of blood were taken at various intervals for 2 days and the 3H, 35S, and 14C concentra-tions in DS in the plasma samples were determined. The concentrations of unlabeled DS in plasma were also determined. On the basis of a two-pool (D and DS) model and using equa-tions presented in the preceding paper, valuesfor the volume of distribution of DS, the metabolic clearance rate of DS in plasma, the production rate of plasma DS, the rate of conversion of DS to D, and the rate of excretion and conversion of DS to other products were estimated. Urine was collected for 3 days after the injection and the specific activities of DS and dehydroisoandrosterone glucuronide (DG) isolated from the urine were determined. From these specific activities the rates of secretion and metabolism of DS and of D were estimated. Where com-parisons were possible, it was found that the values of the parameters related to themetabolism of DS obtained from plasma data did not significantly differ from those obtained from urinary data. In another experiment the same mixture of tracers was injected into a normal male and blood samples were taken at short intervals during 2 hours following the injection. In this case, the existence of another sulfate pool exchanging with DS in plasma was detected. Its influence on the interpretation of the results obtained from the female subject is discussed.That dehydroisoandrosterone sulfate (DS) 1 may have a greater physiological importance than that of a mere urinary metabolite is suggested by several recent find-ings. For example DS, the most abundant steroid in plasma, has been shown to be produced by adrenal tissue both in vivo (Baulieu, 1962; VandeWiele et al., 1963) and under in vitro conditions (Wallace and Lieber-man, 1963; Cohn et al., 1963; Migeon, 1963). Infact, as far as is known, the secretion of DS by the adrenal is uniquein that no other product of an endocrine gland is known to be secreted in a conjugated form. Also characteristic is the fact that DS and free dehydroisoandrosterone (D) are interconvertible in normal circum-stances (Roberts et al., 1961). Human placental tissue has been shown (Warren and Timberlake, 1962) to con-vert DS to D, and more surprisingly, the studies of Siiteri and MacDonald (1963) and of Baulieu and Dray (1963) have shown that, in pregnant women, circulating DS is efficiently converted to estrogens. Moreover, the implication that steroidsulfates may have a function other than an excretory one received added support from the work of Calvin (Calvin et al., 1963; Calvin and Lieberman, 1964) who have shown that such con-jugates undergo biosynthetic reactions similar to those involved in the formation of steroids customarily con-sidered to be hormones. These facts emphasize the de-sirability of obtaining additional quantitative information about such conjugates, particularly DS.