Hormone-regulated expression and distribution of versican in mouse uterine tissues.
BACKGROUND
Remodeling of the extracellular matrix is one of the most striking features observed in the uterus during the estrous cycle and after hormone replacement. Versican (VER) is a hyaluronan-binding proteoglycan that undergoes RNA alternative splicing, generating four distinct isoforms. This study analyzed the synthesis and distribution of VER in mouse uterine tissues during the estrous cycle, in ovariectomized (OVX) animals and after 17beta-estradiol (E2) and medroxyprogesterone (MPA) treatments, either alone or in combination.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Salgado
Renato M
RM
Laboratory of Reproductive and Extracellular Matrix Biology, Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil. rsalgado@icb.usp.br
Capelo
Luciane P
LP
Favaro
Rodolfo R
RR
Glazier
Jocelyn D
JD
Aplin
John D
JD
Zorn
Telma M T
TM
D000818:Animals; D004031:Diestrus / Q000502:physiology; D004967:Estrogens / Q000378:metabolism / Q000494:pharmacology; D030762:Estrous Cycle / Q000502:physiology*; D004971:Estrus / Q000502:physiology; D005260:Female; D007124:Immunoenzyme Techniques; D008525:Medroxyprogesterone / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D011359:Proestrus / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014599:Uterus / Q000187:drug effects / Q000502:physiology*; D053675:Versicans / Q000235:genetics* / Q000378:metabolism*
D004967:Estrogens; D012333:RNA, Messenger; C508323:Vcan protein, mouse; D053675:Versicans; D008525:Medroxyprogesterone