NON-GENOMIC EFFECTS OF CATECHOLESTROGENS IN THE IN-VITRO RAT UTERINE CONTRACTION

1. The effects of catecholestrogens 2-hydroxyestradiol (2-OH E(2), 0.6-30 mu M), 4-hydroxyestradiol (4-OH E(2), 1-30 mu M) and 2-methoxyestradiol (2-MeO E(2), 0.6-30 mu M) 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 EC(50)s were: 4.4 +/- 0.5, 4.2 +/- 0.3 and 8.5 +/- 0.7 mu M for 2-MeO E(2), 2-OH E(2) and 4-OH E(2), respectively. This relaxing effect was counteracted by CaCl2 (1-10 mM) but not by the calcium channel agonist Bay k 8644 (1 nM-1 mu M). 3. The effect of 2-MeO E(2) is not modified by propranolol (1 mu M), cycloheximide (35 mu M), actinomycin D (4 mu M), alpha-difluoromethyl-ornithine (10 mM) or genistein (10 mu M). Nor did cycloheximide (35 mu M) or actinomycin D (4 mu M) modify the relaxing effect of 2-OH E(2) and 4-OH E(2). Propranolol (1 mu M) significantly increased the effect of 4-OH E(2) but not the effect of 2-OH E(2). 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.