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

Francisco M Pinto,Luz Candenas,Jocelyn N Pennefather,C Oscar Pintado,Eva Patak

doi:10.1186/1477-7827-7-77

Abstract

BackgroundIn the mouse uterus, pregnancy is accompanied by changes in tachykinin and tachykinin receptor gene expression and in the uterotonic effects of endogenous tachykinins. In this study we have investigated whether changes in tachykinin expression and responses are a result of changes in ovarian steroid levels.MethodsWe 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.ResultsAll 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.ConclusionThese 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.

Highlights

In the mouse uterus, pregnancy is accompanied by changes in tachykinin and tachykinin receptor gene expression and in the uterotonic effects of endogenous tachykinins
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 [2,3,4,5,6,7]. In addition to these classical genotropic effects, E2 and P4 activate extranuclear, nongenomic signaling cascades [8,9]. It is still unclear whether non-genomic effects are mediated by membrane receptors distinct from the nuclear receptors, or involve activation of classical ERs or PRs located outside the nucleus [4,5,6,7,8,9]
We have previously found that all genes encoding TKs and their receptors are expressed in the mammalian uteri and that their expression and function vary during the ovarian cycle, throughout pregnancy and with age, [3,10,29,30,38,39]

Summary

Introduction

Pregnancy is accompanied by changes in tachykinin and tachykinin receptor gene expression and in the uterotonic effects of endogenous tachykinins. 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 [2,3,4,5,6,7]. In addition to these classical genotropic effects, E2 and P4 activate extranuclear, nongenomic signaling cascades [8,9]. It is still unclear whether non-genomic effects are mediated by membrane receptors distinct from the nuclear receptors, or involve activation of classical ERs or PRs located outside the nucleus [4,5,6,7,8,9]

Methods

Results

Discussion

Conclusion