Progesterone Metabolites Inhibit the Human Ether-a-go-go-Related Gene and Predict QT Interval Length.

ABSTRACT: A decrease in the human ether-a-go-go-related gene (hERG/KCNH2)-related channel has been linked to intrauterine fetal death. The formation of cytochrome P450 (CYP) 3A-mediated progesterone metabolites, 6-beta-hydroxy-progesterone (6β-OHP) and 16α-hydroxy-progesterone (16α-OHP), is variable among adults and differs from fetal metabolism. The primary objective of this study was to assess the potential for progesterone metabolites to inhibit hERG-related current and predict QTc intervals. Whole-cell voltage-clamp electrophysiology was performed on human embryonic kidney 293 cells stably expressing hERG exposed to progesterone or metabolites. Both 6β-OHP and 16α-OHP positively shifted the voltage dependence of activation relative to vehicle from -4.0 ± 0.8 to -0.3 ± 0.8 mV, P < .01; and 1.0 ±

SUBMITTER: Shugg T 

PROVIDER: S-EPMC10170396 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature