title: Metabolism of 17-alpha-hydroxyprogesterone caproate by human placental mitochondria.
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 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.
authors.affiliation: Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Valentina M
authors.initials: VM
authors.lastname: Fokina
authors.forename: Olga L
authors.initials: OL
authors.lastname: Zharikova
authors.forename: Gary D V
authors.initials: GD
authors.lastname: Hankins
authors.forename: Mahmoud S
authors.initials: MS
authors.lastname: Ahmed
authors.forename: Tatiana N
authors.initials: TN
authors.lastname: Nanovskaya
mesh_terms: D000077713:17 alpha-Hydroxyprogesterone Caproate; D005260:Female; D006801:Humans; D006908:Hydroxyprogesterones / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy
chemical_list: D006908:Hydroxyprogesterones; D000077713:17 alpha-Hydroxyprogesterone Caproate