Metabolism of 17-Alpha-Hydroxyprogesterone Caproate by Human Placental Mitochondria
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.
Keywords17-alpha-hydroxyprogesterone caproate metabolism placenta mitochondria LC-MS
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- 7.Clement B, Mau S, Debers S, Havemeyer A. Hepatic, extrahepatic, microsomal, and mitochondrial activation of the N-hydroxylated prodrugs benzamidoxime, guanoxabenz, and RO 48-3656 ([[1-[(2S)-2-[[4-[(hydroxyamino)iminomethyl]benzoyl]amino]-1-oxopropyl]-4-piperidinyl]oxy]-actic acid). Drug Metab Dispos. 2005; 33(11):1740–1747.CrossRefGoogle Scholar
- 8.da Fonseca EB, Bittar RE, Carvalho MH, Zugaib M. Prophylactic administration of progesterone by vaginal suppository to reduce the incidence of spontaneous preterm birth in women at increased risk: a randomized placebo-controlled double-blind study. Am J Obstet Gynecol. 2003;188(2):419–424.CrossRefGoogle Scholar
- 10.Sexton DJ, O’Reilly MW, Friel AM, Morrison JJ. Functional effects of 17alpha hydroxyprogesterone caproate (17P) on human myometrial contractility in vitro. Reprod Biol Endocrinol. 2004; 2:80.Google Scholar