Ovarian steroids regulate tachykinin and tachykinin receptor gene expression in the mouse uterus

We quantified the mRNAs of tachykinins and tachykinin receptors in uteri from ovariectomized mice and studied their regulation in response to estrogen and progesterone using real-time quantitative RT-PCR. Early (3 h) and late (24 h) responses to estrogen were evaluated and the participation of the estrogen receptors (ER), ERalpha and ERbeta, was analyzed by treating mice with propylpyrazole triol, a selective ERalpha agonist, or diarylpropionitrile, a selective agonist of ERbeta.All genes encoding tachykinins (Tac1, Tac2 and Tac4) and tachykinin receptors (Tacr1, Tacr2 and Tacr3) were expressed in uteri from ovariectomized mice. Estrogen increased Tac1 and Tacr1 mRNA after 3 h and decreased Tac1 and Tac4 expression after 24 h. Tac2 and Tacr3 mRNA levels were decreased by estrogen at both 3 and 24 h. Most effects of estrogen were also observed in animals treated with propylpyrazole triol. Progesterone treatment increased the levels of Tac2.These results show that the expression of tachykinins and their receptors in the mouse uterus is tightly and differentially regulated by ovarian steroids. Estrogen effects are mainly mediated by ERalpha supporting an essential role for this estrogen receptor in the regulation of the tachykinergic system in the mouse uterus.Uterine function is tightly controlled by ovarian steroids [1-5]. The physiological responses to acute estrogen (E2) occur in two temporally distinct steps. Early responses appear within the first 2–3 h after E2 administration while late responses are observed 16–24 h after E2, with each step involving activation of distinct sets of genes [4,5]. E2 and progesterone (P4) exert their effects by binding to specific transcription factor receptors, the estrogen receptors α (ERα) and β (ERβ) and the progesterone receptors (PR A and B), respectively [2-7]. In addition to these classical genotropic effects, E2 and P4 activate extranuclear, non-genomic signaling cascades [8,9]. It is still unclear whether non-genomic effe