Investigation prostaglandin of the role of estrogenic action and E2 in DDT-stimulated rat uterine contractions ex vivo

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 E 2 (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 PGE 2 levels in the muscle bath showed no significant differences between control and DDT-treated strips, although significant amounts of PGE 2 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-/3-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 PGE 2 release or direct estrogen receptorrelated action.