Aims: In the present study, we investigated expression, distribution and regulation of oestrogen receptors (ERs) alpha and beta and their modulation by ormeloxifene (Orm) during the period of uterine receptivity in rat uterus in order to determine their role in endometrial sensitization.
Methods: Uterine tissues of control and Orm-treated (1.25 mg kg(-1), orally) rats were collected on days 3, 4, 5 morning and day 5 evening post-coitum referring to non-receptive, pre-receptive and receptive phases respectively. mRNA and protein expression levels were determined by RT-PCR and Western blot respectively. Immunohistochemical technique was used to localize the receptors.
Results: RT-PCR analysis revealed that ERalpha mRNA reached a peak level on day 5 morning whereas ERbeta mRNA expression was found to be very low. In Orm-treated rats, the ERalpha mRNA was suppressed at day 5. The protein expression of ERalpha increased after day 3 and that of ERbeta remained very low throughout the pre-implantation period; Orm caused a decrease in ERalpha on day 5 morning. In endometrium, ERalpha expression was regulated differentially in luminal epithelium, glandular epithelium and stroma. Orm caused a decrease in the percentage of ERalpha-positive nuclei in all the three endometrial compartments on days 4 and 5, and the magnitude of reduction varied spatio-temporally. In case of ERbeta, immunostaining was not detectable in Orm-treated and control groups.
Conclusion: It appears that the complex uterine response to implantation is governed by differential cell-specific ERalpha expression. The study suggested the inhibitory activity of Orm on ERalpha during the period of uterine receptivity.