Hormone-regulated expression and distribution of versican in mouse uterine tissues

Uteri from mice in all phases of the estrous cycle, and animals subjected to ovariectomy and hormone replacement were collected for immunoperoxidase staining for versican, as well as PCR and quantitative Real Time PCR.In diestrus and proestrus, VER was exclusively expressed in the endometrial stroma. In estrus and metaestrus, VER was present in both endometrial stroma and myometrium. In OVX mice, VER immunoreaction was abolished in all uterine tissues. VER expression was restored by E2, MPA and E2+MPA treatments. Real Time PCR analysis showed that VER expression increases considerably in the MPA-treated group. Analysis of mRNA identified isoforms V0, V1 and V3 in the mouse uterus.These results show that the expression of versican in uterine tissues is modulated by ovarian steroid hormones, in a tissue-specific manner. VER is induced in the myometrium exclusively by E2, whereas MPA induces VER deposition only in the endometrial stroma.The estrous cycle is orchestrated by ovarian sex hormones [1]. In the mature mouse, estrogen (E2) produced during estrus stimulates epithelial cell proliferation and synthesis of progesterone receptors (PR). On the other hand, progesterone (P4) inhibits epithelial proliferation while stimulating the multiplication of stromal cells that characterizes the beginning of decidualization [2,3]. The combined action of E2 and P4 prepares uterine tissues for blastocyst implantation.Estrogen receptors (ERα and ERβ) and progesterone receptors (PRA, PRB and PRC) are transcription factors that regulate gene expression by direct binding to DNA regulatory sequences and by specific interactions with co-activators and/or co-repressor proteins [4,5]. In response to the normal changes in the levels of E2 and P4, the endometrium and myometrium undergo extensive cellular and extracellular modification [6].The ECM is a complex structure of macromolecules capable of self-assembly and is composed predominantly of collagens, non-collagenous multiadhesive glycop