The use of constant infusion of unlabeled dehydroepiandrosterone for the assessment of its metabolic clearance rate, its half-life, and its conversion into estrogens.

The use of constant infusion of unlabeled dehydroepiandrosterone for the assessment of its metabolic clearance rate, its half-life, and its conversion into estrogens.
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使用持续输注未标记的脱氢表雄酮来评估其代谢清除率、半衰期及其向雌激素的转化。

DOI:
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发表时间:
1980
影响因子:
5.8
通讯作者:
D. Tulchinsky
D. Tulchinsky
中科院分区:
医学2区
文献类型:
--
作者:
S. Bélisle;I. Schiff;D. Tulchinsky

文献摘要

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我们利用持续输注未标记的脱氢表雄酮 (DHEA) 来计算其 MCR、半衰期 (t1/2) 及其向雌激素的转化率的可行性。在非孕妇中,输注未标记的 DHEA 所获得的结果与输注标记的类固醇或标记和未标记的类固醇的混合物所获得的结果相似。输注速率增加 3 倍并没有改变任何这些结果,表明酶的可用性并不是从 DHEA 生产雌二醇 (E2) 的限制步骤。与非妊娠状态相比,足月妊娠与血浆 DHEA 浓度的变化无关,但 DHEA 的 MCR 为 76.8 +/- 18.8 (SE) 升/kg·天,高 2.5 倍,t1/2 为 22.5 +/- 3.6 分钟,低 2 倍。怀孕期间DHEA转化为E2的比例增加了500倍,DHEA贡献了母体循环E2的9%。产后第一天,DHEA的MCR及其t1/2与足月妊娠没有显着差异,表明妊娠期DHEA的MCR增加不仅仅是由于胎盘清除DHEA的增加。
We have exploited the feasibility of utilizing constant infusion of unlabeled dehydroepiandrosterone (DHEA) for calculating its MCR, its half-life (t1/2), and its conversion ratio into estrogens. In nonpregnant women, results obtained by infusion of unlabeled DHEA were similar to those obtained by the infusion of either labeled steroid or a mixture of labeled and unlabeled steroid. An increase of 3-fold in the infusion rate did not change any of these results, indicating that enzyme availability was not a limiting step in the production of estradiol (E2) from DHEA. When compared to the nonpregnancy state, term pregnancy was not associated with a change in plasma DHEA concentrations, but the MCR of DHEA of 76.8 +/- 18.8 (SE) liters/kg.day was 2.5-fold higher and the t1/2 of 22.5 +/- 3.6 min was 2-fold lower. The conversion ratio of DHEA into E2 increased during pregnancy by 500-fold, and DHEA contributed 9% of maternal circulating E2. In the first postpartum day, the MCR of DHEA and its t1/2 were not significantly different from those of term pregnancy, suggesting that the increased MCR of DHEA in pregnancy was not solely due to increased clearance of DHEA by the placenta.