Prostaglandin receptors EP and FP are regulated by estradiol and progesterone in the uterus of ovariectomized rats

We performed four different rat experiments involving treatments with estradiol, progesterone and ER agonists. Real-time PCR and immunohistochemistry were employed to evaluate receptor expression.Our results showed that all mRNAs and proteins of EPs and FP are expressed in the rat uterus. The expression pattern and intensity of immunostaining vary between different cell types and treatments. The mRNA expression of all EPs and FP are downregulated by estradiol and the ERalpha specific agonist PPT, whereas the ERbeta specific agonist DPN downregulates only EP2 and EP4. The protein expression however, showed an increase in EP2 and EP3 after estradiol treatment. When treated with estradiol and progesterone in combination, the expressions of EP1 and EP3 are upregulated.Regulation of EPs and FP expression by estradiol appears to be mainly modulated via ERalpha for EP1, EP3 and FP, while EP2 and EP4 also are affected by the ERbeta selective ligand. Our immunohistochemical data shows a cell specific regulation of prostaglandin receptors under the influence of ovarian steroids, where EP2 is estrogen regulated in all uterine tissues examined. EP1 and EP3 are upregulated by the combination of estradiol and progesterone. Thus, our observations indicate that estradiol and progesterone regulate the mRNA and protein expression of EPs and FP in a receptor and tissue specific way.Prostaglandins are inflammatory mediators that play an important role in female reproduction [1-5]. Prostaglandin (PG) receptors are heptahelical transmembrane G protein coupled receptors and are expressed in cytoplasmic membranes [6,7]. PGE2 transduces its signal through four different receptor subtypes, EP1, EP2, EP3 and EP4 whereas the action of PGF2α is mediated by FP [8,9]. These receptors have a distinct differential affinity to ligands, biochemical properties and tissue localization [8]. PGE2 and PGF2α are key factors in female reproduction with vital functions in blastocyst spacing, implantation, de