A non-genomic signaling pathway shut down by mating changes the estradiol-induced gene expression profile in the rat oviduct

Estradiol (E₂) accelerates oviductal egg transport through intraoviductal non-genomic pathways in unmated rats and through genomic pathways in mated rats. This shift in pathways has been designated as intracellular path shifting (IPS), and represents a novel and hitherto unrecognized effect of mating on the female reproductive tract. We had reported previously that IPS involves shutting down the E₂ non-genomic pathway up- and downstream of 2-methoxyestradiol. Here, we evaluated whether IPS involves changes in the genomic pathway too. Using microarray analysis, we found that a common group of genes changed its expression in response to E₂ in unmated and mated rats, indicating that an E₂ genomic signaling pathway is present before and after mating; however, a group of genes decreased its expression only in mated rats and another group of genes increased its expression only in unmated rats. We evaluated the possibility that this difference is a consequence of an E₂ non-genomic signaling pathway present in unmated rats, but not in mated rats. Mating shuts down this E₂ non-genomic signaling pathway up- and downstream of cAMP production. The Star level is increased by E₂ in unmated rats, but not in mated rats. This is blocked by the antagonist of estrogen receptor ICI 182 780, the adenylyl cyclase inhibitor SQ 22536, and the catechol-O-methyltransferase inhibitor, OR 486. These results indicate that the E₂-induced gene expression profile in the rat oviduct differs before and after mating, and this difference is probably mediated by an E₂ non-genomic signaling pathway operating on gene expression only in unmated rats.