Non-genomic effects of catecholestrogens in the in vitro rat uterine contraction

Abstract

1. The effects of catecholestrogens 2-hydroxyestradiol (2-OH E2, 0.6-30 microM), 4-hydroxyestradiol (4-OH E2, 1-30 microM) and 2-methoxyestradiol (2-MeO E2, 0.6-30 microM) on rat uterine contraction induced by KCl (60 mM), have been assayed. 2. All drugs assayed relaxed the tonic-contraction induced by KCl in a concentration-dependent way. The EC50s were: 4.4 +/- 0.5, 4.2 +/- 0.3 and 8.5 +/- 0.7 microM for 2-MeO E2, 2-OH E2 and 4-OH E2, respectively. This relaxing effect was counteracted by CaCl2 (1-10 mM) but not by the calcium channel agonist Bay k 8644 (1 nM-1 microM). 3. The effect of 2-MeO E2 is not modified by propranolol (1 microM), cycloheximide (35 microM), actinomycin D (4 microM), alpha-difluoromethyl-ornithine (10 mM) or genistein (10 microM). Nor did cycloheximide (35 microM) or actinomycin D (4 microM) modify the relaxing effect of 2-OH E2 and 4-OH E2. Propranolol (1 microM) significantly increased the effect of 4-OH E2 but not the effect of 2-OH E2. 4. Our results suggest that the relaxing effect of catecholestrogens in the rat uterus is a non-genomic effect and could be related to inhibition of extracellular calcium entry.