Patil, Avinash S.Swamy, Geeta K.Murtha, Amy P.Heine, R. PhillipsZheng, XiaomeiGrotegut, Chad A.2016-06-232016-06-232015-12Patil, A. S., Swamy, G. K., Murtha, A. P., Heine, R. P., Zheng, X., & Grotegut, C. A. (2015). Progesterone Metabolites Produced by Cytochrome P450 3A Modulate Uterine Contractility in a Murine Model. Reproductive Sciences, 22(12), 1577–1586. http://doi.org/10.1177/1933719115589414https://hdl.handle.net/1805/10138Objective: We seek to characterize the effect of progesterone metabolites on spontaneous and oxytocin-induced uterine contractility. Study Design: Spontaneous contractility was studied in mouse uterine horns after treatment with progesterone, 2α-hydroxyprogesterone, 6β-hydroxyprogesterone (6β-OHP), 16α-hydroxyprogesterone (16α-OHP), or 17-hydroxyprogesterone caproate (17-OHPC) at 10−9 to 10−6 mol/L. Uterine horns were exposed to progestins (10−6 mol/L), followed by increasing concentrations of oxytocin (1-100 nmol/L) to study oxytocin-induced contractility. Contraction parameters were compared for each progestin and matched vehicle control using repeated measures 2-way analysis of variance. In vitro metabolism of progesterone by recombinant cytochrome P450 3A (CYP3A) microsomes (3A5, 3A5, and 3A7) identified major metabolites. Results: Oxytocin-induced contractile frequency was decreased by 16α-OHP (P = .03) and increased by 6β-OHP (P = .05). Progesterone and 17-OHPC decreased oxytocin-induced contractile force (P = .02 and P = .04, respectively) and frequency (P = .02 and P = .03, respectively). Only progesterone decreased spontaneous contractile force (P = .02). Production of 16α-OHP and 6β-OHP metabolites were confirmed in all CYP3A isoforms tested. Conclusion: Progesterone metabolites produced by maternal or fetal CYP3A enzymes influence uterine contractility.enPublisher Policypreterm laborprogesteroneArticle