Metabolism of 17-Alpha-Hydroxyprogesterone Caproate by Human Placental Mitochondria

被引:6
作者
Fokina, Valentina M. [1 ]
Zharikova, Olga L. [1 ]
Hankins, Gary D. V. [1 ]
Ahmed, Mahmoud S. [1 ]
Nanovskaya, Tatiana N. [1 ]
机构
[1] Univ Texas Med Branch, Dept Obstet & Gynecol, Galveston, TX 77555 USA
关键词
17-alpha-hydroxyprogesterone caproate; metabolism; placenta; mitochondria; LC-MS;
D O I
10.1177/1933719111419248
中图分类号
R71 [妇产科学];
学科分类号
100211 ;
摘要
Perfusion of 17-alpha-hydroxyprogesterone caproate (17HPC) via the maternal circuit of a dually perfused human placental lobule resulted in the extensive formation of 2 metabolites. On the other hand, human placental microsomes biotransformed 17HPC into 5 monohydroxylated metabolites, which did not correspond to those formed during perfusion. The goal of this investigation was to determine the subcellular localization of the enzymes responsible for the biotransformation of 17HPC during its perfusion in human placenta. Crude subcellular fractions of the human placental tissue were utilized. Six 17HPC metabolites were formed by the placental mitochondrial fraction, of which 4 were identical to those formed by the microsomes; whereas the other 2, namely MM and M19, were formed by the mitochondrial fraction only. The latter metabolites were identical to those formed during 17HPC perfusion, as determined by liquid chromatography-mass spectrometry (LC-MS) analysis. Therefore, these data strongly suggest that the enzymes responsible for the biotransformation of 17HPC during its perfusion are predominantly localized in human placental mitochondria.
引用
收藏
页码:290 / 297
页数:8
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