title: Resveratrol and endometrium: a closer look at an active ingredient of red wine using in vivo and in vitro models.
abstract: Resveratrol is a natural phytoestrogen with antiproliferative properties present in red wine, grapes, and berries. Published reports on the effects of resveratrol in human endometrial function are limited. The objective of this study was to investigate the expression of estrogen receptor α (ESR1), Ki-67 (a proliferative marker), aryl hydrocarbon receptor (AhR), and members of the cytochrome P450 superfamily of enzymes (CYP1A1 and CYP1B1) in an in vitro and vivo assay. Alkaline phosphatase assay of estrogenicity was used to compare estrogen activity of different concentrations of resveratrol to estradiol (E2) and diethylstilbestrol (DES), using Ishikawa cell culture. Immunohistochemical expression of ESR1 and Ki67, and reverse transcriptase polymerase chain reaction of AhR, CYP1A1, and CYP1B1 were analyzed from xenograft implants of human endometrial tissue in ovariectomized immunodeficient RAG-2-γ(c) mice, after 30 days of treatment with subcutaneous pellets of E2, E2 plus progesterone (P4), or E2 plus resveratrol (6, 30, or 60 mg) for 30 days. Compared to E2, resveratrol acted as an agonist and antagonist of estrogen in low and high concentrations, respectively, when combined with E2. Xenografts of human endometrial tissues in RAG-2 mice exhibited reduced expression of ESR1 and proliferative activity (Ki67) with 60 mg of resveratrol. This study suggests that resveratrol, at high doses, has the potential benefit to reduce proliferation of human endometrium through ESR1.
authors.affiliation: Department of Obstetrics and Gynecology, Greenville Health System, Greenville, SC, USA.
authors.forename: S C
authors.initials: SC
authors.lastname: Amaya
authors.affiliation: Departmento de Ginecologia e Obstetrícia, Universidade Federal do Rio Grande do Sul, Brazil Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill, NC, USA.
authors.forename: R F
authors.initials: RF
authors.lastname: Savaris
authors.affiliation: Department of Obstetrics and Gynecology, Greenville Health System, Greenville, SC, USA.
authors.forename: C J
authors.initials: CJ
authors.lastname: Filipovic
authors.affiliation: Department of Obstetrics and Gynecology, Greenville Health System, Greenville, SC, USA Department of Biology, Furman University, Greenville, SC, USA.
authors.forename: J D
authors.initials: JD
authors.lastname: Wise
authors.affiliation: Department of Obstetrics and Gynecology, Greenville Health System, Greenville, SC, USA Department of Biology, Furman University, Greenville, SC, USA.
authors.forename: E
authors.initials: E
authors.lastname: Hestermann
authors.affiliation: Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill, NC, USA.
authors.forename: S L
authors.initials: SL
authors.lastname: Young
authors.affiliation: Department of Obstetrics and Gynecology, Greenville Health System, Greenville, SC, USA blessey@ghs.org.
authors.forename: B A
authors.initials: BA
authors.lastname: Lessey
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism; D065633:Cytochrome P-450 CYP1B1 / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics; D004054:Diethylstilbestrol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004717:Endometrium / Q000187:drug effects* / Q000637:transplantation; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000187:drug effects / Q000378:metabolism; D005260:Female; D064593:Heterografts; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010052:Ovariectomy; D048789:Phytoestrogens / Q000494:pharmacology*; D018336:Receptors, Aryl Hydrocarbon / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D013997:Time Factors; D014920:Wine
chemical_list: D000469:Alkaline Phosphatase; D051792:Basic Helix-Loop-Helix Proteins; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1; D004268:DNA-Binding Proteins; D004054:Diethylstilbestrol; D004958:Estradiol; D047628:Estrogen Receptor alpha; D019394:Ki-67 Antigen; D048789:Phytoestrogens; D018336:Receptors, Aryl Hydrocarbon; D000077185:Resveratrol; D013267:Stilbenes; C111235:AHR protein, human; C506487:ESR1 protein, human; C499308:Rag2 protein, mouse; C569463:CYP1A1 protein, human; C585496:CYP1B1 protein, human
keywords: Ishikawa; cell proliferation; endometriosis; estrogen receptor; human endometrium; resveratrol