Expression of oestrogen receptors α and β during the period of uterine receptivity in rat:: effect of ormeloxifene, a selective oestrogen receptor modulator

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 ER alpha mRNA reached a peak level on day 5 morning whereas ER beta mRNA expression was found to be very low. In Orm-treated rats, the ER alpha mRNA was suppressed at day 5. The protein expression of ER alpha increased after day 3 and that of ER beta remained very low throughout the pre-implantation period; Orm caused a decrease in ER alpha on day 5 morning. In endometrium, ER alpha expression was regulated differentially in luminal epithelium, glandular epithelium and stroma. Orm caused a decrease in the percentage of ER alpha-positive nuclei in all the three endometrial compartments on days 4 and 5, and the magnitude of reduction varied spatio-temporally. In case of ER beta, 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 ER alpha expression. The study suggested the inhibitory activity of Orm on ER alpha during the period of uterine receptivity.