期刊
REPRODUCTIVE SCIENCES
卷 22, 期 12, 页码 1577-1586出版社
SAGE PUBLICATIONS INC
DOI: 10.1177/1933719115589414
关键词
16-hydroxyprogesterone; 6-hydroxyprogesterone; 17-hydroxyprogesteone caproate; preterm labor; progesterone
资金
- NIH-NIGMS [T32 GM 86330-1 A1]
Objective: 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, 2-hydroxyprogesterone, 6-hydroxyprogesterone (6-OHP), 16-hydroxyprogesterone (16-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 16-OHP (P = .03) and increased by 6-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 16-OHP and 6-OHP metabolites were confirmed in all CYP3A isoforms tested. Conclusion: Progesterone metabolites produced by maternal or fetal CYP3A enzymes influence uterine contractility.
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