This Article Full Text Full Text (PDF) All Versions of this Article: 22/4/904    most recent Author Manuscript (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager NURSA Molecule Pages Link Google Scholar Articles by Utsunomiya, H. Articles by Bulun, S. E. PubMed PubMed Citation Articles by Utsunomiya, H. Articles by Bulun, S. E.

Upstream Stimulatory Factor-2 Regulates Steroidogenic Factor-1 Expression in Endometriosis

Division of Reproductive Biology Research (H.U., Y.-H.C., Z.L., S.R., P.Y., E.A., Q.X., G.I., S.T., E.T., J.J.K., S.E.B.), Department of Obstetrics and Gynecology, Feinberg School of Medicine at Northwestern University, Illinois 60611; and Departments of Pathology (T.S., H.S.) and Obstetrics and Gynecology (N.Y.), Tohoku University School of Medicine, 980-8574 Sendai, Japan

Address all correspondence and requests for reprints to: Serdar E. Bulun, Division of Reproductive Biology Research, Feinberg School of Medicine, Northwestern University, 303 Superior Street, Suite 4-123, Chicago, Illinois 60611. E-mail: s-bulun{at}northwestern.edu.

Local estrogen biosynthesis is a major factor in the pathogenesis of endometriosis. Aberrant expression of steroidogenic acute regulatory protein (StAR) and aromatase in endometriotic tissue leads to an up-regulation of estrogen production. The transcription factor steroidogenic factor-1 (SF-1) activates the promoters of both StAR and aromatase in endometriotic tissue. We investigated differences in SF-1 expression in endometriotic tissue and normally located endometrium to elucidate the mechanism underlying increased StAR and aromatase activities in endometriosis. Serial deletion and site-directed mutants of the SF-1 promoter showed that an E-box sequence was critical for its activity in endometriotic stromal cells. EMSAs showed that the upstream stimulatory factor (USF) 1 and 2 in nuclear extracts from endometrial and endometriotic stromal cells bound to the E-box. Chromatin-immunoprecipitation-PCR assay, however, demonstrated in intact cells that binding activity of USF2 to the SF-1 promoter was strikingly higher than that of USF1 in endometriotic stromal cells and that USF1 or USF2 binding activity was hardly detectable in endometrial stromal cells. Moreover, knockdown of USF2 but not USF1 resulted in robust and consistent down-regulation of SF-1 and its target genes StAR and aromatase in endometriotic stromal cells. USF2 but not USF1 mRNA and protein levels were significantly higher in endometriotic vs. endometrial stromal cells. In vivo, USF2 mRNA and immunoreactive USF2 levels in endometriotic tissues were strikingly higher than those in endometrium. Taken together, the elevated levels of USF2 in endometriosis account for, in part, the aberrant expression of SF-1 and its target gene StAR and aromatase.

NURSA Molecule Pages Link:

Nuclear Receptors:   SF-1