Metabolism of 17-alpha-hydroxyprogesterone caproate by human placental mitochondria

Valentina M. Fokina, Olga L. Zharikova, Gary D.V. Hankins, Mahmoud S. Ahmed, Tatiana N. Nanovskaya

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

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 M 19, 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.

Original languageEnglish (US)
Pages (from-to)290-297
Number of pages8
JournalReproductive Sciences
Volume19
Issue number3
DOIs
StatePublished - Mar 2012

Keywords

  • 17-alpha-hydroxyprogesterone caproate
  • LC-MS
  • metabolism
  • mitochondria
  • placenta

ASJC Scopus subject areas

  • Obstetrics and Gynecology

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