Evidence that 5β‐progestins produce uterine relaxation by diminishing cellular calcium permeability

This report presents the relaxant effect of progesterone and some of its 5β‐derivatives on the tonic contractions induced in isolated rat uterus by high K+ (40 mM) and high K+Na+‐free depolarizing solutions. Experiments were recorded with a polygraphic system. Contractions were countered by the action of progesterone (101 μM), pregnanedione (41 μM), pregnanolone (25 μM), and epipregnanolone (47 μM). The relaxant effect of progestins was, however, significantly more effective against the contraction produced by high K+ alone than that produce by high K+Na+‐free solutions. These different results suggest the ability of 5β‐reduced progesterone metabolites to block the sensitive‐to‐voltage Ca2+ channels (which are activated by K+) and also agree with the existence of a Na+/Ca2+ interchanger in the myometrial membrane. It can be concluded that 5β‐progestins induce relaxation of the uterus probably by blocking the calcium entrance into the cell.