Rat Uterine Oxytocin Receptor and Estrogen Receptor α and β mRNA Levels are Regulated by Estrogen Through Multiple Estrogen Receptors

Estrogen action is mediated through several types of receptors (ERs), such as ER alpha, ER beta and putative membrane ERs. Oxytocin receptor (OTR) and ER expression levels in the rat uterus are regulated by estrogen; however, which types of ERs are involved has not been elucidated. This study examined OTR, ERa and ER beta levels in ovariectomized rats treated with 17 beta-estradiol (E2), an ER alpha agonist (PPT), an ER beta agonist (DPN) or estren (Es). E2 and PPT increased OTR mRNA levels and decreased ER alpha and ER beta mRNA levels 3 and 6 h posttreatment. DPN decreased ER alpha and ER beta mRNA levels at 3 and 6 h, while OTR mRNA levels increased at 3 h and decreased at 6 h. OTR mRNA levels increased 3 h after the Es treatment and then declined until 6 h. ER alpha and ER beta mRNA levels decreased by 3 h and remained low until 6 h posttreatment with Es. The ER antagonist ICI182,780 (ICI) suppressed the increases in OTR mRNA levels induced 3 h after the Es treatment. However, ICI and tamoxifen (Tam) had no significant effect on ER alpha and ER beta mRNA levels in the Es-treated or vehicle-treated group. In intact rats, proestrus-associated increases in OTR mRNA levels were antagonized by both ICI and Tam. However, decreases in ER alpha and ER beta mRNA levels were not antagonized by Tam and ICI, respectively. Therefore, uterine OTR gene expression is upregulated by estrogen through the classical nuclear (or non-nuclear) ERs, ER alpha and ER beta while the levels of these ERs are downregulated by estrogen through multiple pathways including Es-sensitive nonclassical ERs.