INVESTIGATION OF THE ROLE OF ESTROGENIC ACTION AND PROSTAGLANDIN-E2 IN DDT-STIMULATED RAT UTERINE CONTRACTIONS EXVIVO

Previous work in our laboratory showed that o,p'-DDT increases the frequency of rat uterine contractions in vitro. The present study investigated whether this response was related to prostaglandin E2 (PGE2) release from the uterine strips or to the estrogenicity of o,p'-DDT. Contraction frequency was evaluated by recording isometric spontaneous contractions in longitudinal uterine strips from pregnant rats. Assessment of PGE2 levels in the muscle bath showed no significant differences between control and DDT-treated strips, although significant amounts of PGE2 were detected in both groups and increased contraction frequency was observed in o,p'-DDT-treated strips. Furthermore, a role for direct estrogenic action in the mediation of o,p'-DDT-stimulated uterine contraction was not supported by the contractility data, because: (i) unlike o,p'-DDT, 17-beta-estradiol had no stimulatory effect, but instead exerted a significant inhibitory effect on uterine contraction; (ii) the estrogen antagonist, tamoxifen, failed to block the stimulatory effect of o,p'-DDT; and (iii) p,p'-DDD, a non-estrogenic DDT analogue, significantly stimulated contraction frequency, similar to o,p'-DDT. These results suggest that the stimulatory effect of o,p'-DDT on contraction frequency is not dependent on PGE2 release or direct estrogen receptor-related action.