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