Genomic and non-genomic effects of steroidal drugs on smooth muscle contraction in vitro.

The effect of steroidal drugs on KCl (60 mM)-induced tonic contraction in in vitro rat uterus has been assayed. Ouabain had no effect and aldosterone only relaxed the KCl contraction up to 27 +/- 7.3%. However, estradiol, testosterone, progesterone, cortisol and alphaxalone relaxed the contraction in a dose-dependent way, and CaCl2 (0.1 to 6 mM) counteracted this effect. Cycloheximide (1 and 10 micrograms/ml) did not modify the effect of progesterone, testosterone or alphaxalone. Cycloheximide, but not actinomycin D (5 micrograms/ml), reduced the effect of cortisol. Both cycloheximide and actinomycin D shifted righward the relaxing effect of estradiol. This suggests that the steroidal relaxing effect in smooth muscle is preferably non-genomic and at plasma membrane level. However, cortisol and estradiol also act at intracellular levels and induce transcriptional (estradiol) or non-transcriptional (cortisol) effects.