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dc.contributor.authorImir, Ayse Gonca
dc.contributor.authorLin, Zhihong
dc.contributor.authorYin, Ping
dc.contributor.authorDeb, Santanu
dc.contributor.authorYilmaz, Bertan
dc.contributor.authorCetin, Meral
dc.contributor.authorCetin, Ali
dc.contributor.authorBulun, Serdar E.
dc.date.accessioned2019-07-27T12:10:23Z
dc.date.accessioned2019-07-28T10:16:40Z
dc.date.available2019-07-27T12:10:23Z
dc.date.available2019-07-28T10:16:40Z
dc.date.issued2007
dc.identifier.issn0021-972X
dc.identifier.issn1945-7197
dc.identifier.urihttps://dx.doi.org/10.1210/jc.2006-2482
dc.identifier.urihttps://hdl.handle.net/20.500.12418/10616
dc.descriptionWOS: 000246221200071en_US
dc.descriptionPubMed ID: 17341559en_US
dc.description.abstractContext: Uterine leiomyomata are common tumors that cause irregular uterine bleeding and pregnancy loss and depend on estrogen for growth. Aromatase catalyzes the conversion of androgens to estrogens. Aromatase expression is regulated via alternatively used promoters in the placenta (I.1 and I.2a), fat (I.4, I.3, and II), bone (I.6), and gonads (II). A prostaglandin E-2/cAMP-dependent pathway regulates coordinately the proximal promoters I.3/II, whereas glucocorticoids and cytokines regulate the distal promoter I.4. Use of each promoter gives rise to a population of aromatase mRNA species with unique 5'-untranslated regions (5'-UTRs). Uterine leiomyoma tissue, but not normal myometrium, overexpresses aromatase leading to estrogen-stimulated cell proliferation. Aromatase inhibitor treatment shrank uterine leiomyomata in a few women. Objective and Design: Promoter I.4 was reported to regulate aromatase expression in uterine leiomyomata from a group of Japanese women. Here, we used two independent techniques to identify the promoters that regulate aromatase expression in uterine leiomyomata (n=30) from 23 African-American, Hispanic, and white women. Results: Rapid amplification of 5'-cDNA ends of aromatase mRNA species revealed the following distribution of promoter usage in leiomyomata: promoters I.3/II, 61.5%; I.2a, 15.4%; I.6, 15.4%; and I.4, 7.7%. Real-time PCR, which quantifies mRNA species with promoter-specific 5'-UTRs, revealed the following distribution for each 5'-UTR as a fraction of total aromatase mRNA: I.3/II, 69.6%; I.4, 7.3%; and other promoters, 23.1%. Conclusions: The primary in vivo aromatase promoter in leiomyoma tissues in non-Asian U.S. women is the prostaglandin E2/cAMP-responsive I.3/II region. Alternative signals may stimulate aromatase expression that is a common biological phenotype in uterine leiomyomata.en_US
dc.description.sponsorshipNICHD NIH HHS [HD 46260]en_US
dc.language.isoengen_US
dc.publisherENDOCRINE SOCen_US
dc.relation.isversionof10.1210/jc.2006-2482en_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.titleAromatase expression in uterine leiomyomata is regulated primarily by proximal promoters I.3/IIen_US
dc.typearticleen_US
dc.relation.journalJOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISMen_US
dc.contributor.departmentNorthwestern Univ, Dept Obstet & Gynecol, Chicago, IL 60611 USA -- Northwestern Univ, Div Reprod Biol Res, Chicago, IL 60611 USA -- Cumhuriyet Univ, Sch Med, Dept Obstet & Gynecol, TR-58140 Sivas, Turkeyen_US
dc.contributor.authorIDCetin, Ali -- 0000-0002-5767-7894; yilmaz, bertan -- 0000-0001-5558-3299en_US
dc.identifier.volume92en_US
dc.identifier.issue5en_US
dc.identifier.endpage1982en_US
dc.identifier.startpage1979en_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US


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