This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 148/10/4875    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 Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Penttinen, P. Articles by Pongratz, I. Search for Related Content PubMed PubMed Citation Articles by Penttinen, P. Articles by Pongratz, I.

Diet-Derived Polyphenol Metabolite Enterolactone Is a Tissue-Specific Estrogen Receptor Activator

Department of Biosciences and Nutrition (P.P., A.E.D., J.I., K.P., I.P.), Karolinska Institute, S-141 57 Huddinge, Sweden; Functional Foods Forum (P.P., S.M.), University of Turku, FI-20520 Turku, Finland; Institute of Physical and Theoretical Chemistry (J.J., G.G.), University of Tuebingen, D-72076 Tuebingen, Germany; Fertility Clinic (J.G.L.), Section 4071, The Rigshospital, 2100 O Copenhagen, Denmark; Netherlands Institute for Developmental Biology (P.v.d.S.), Royal Netherlands Academy of Arts and Sciences, 3584 CT Utrecht, The Netherlands; and Department of Biochemistry and Food Chemistry (S.M.), University of Turku, FI-20500 Turku, Finland

Address all correspondence and requests for reprints to: Dr. Ingemar Pongratz, Department of Biosciences and Nutrition at Novum, Karolinska Institute, Hälsovägen 7, SE-147 51 Huddinge, Sweden. E-mail: inpo{at}biosci.ki.se.

Numerous dietary compounds can modify gene expression by binding to the members of the nuclear receptor superfamily of transcription factors. For example, dietary polyphenols, such as soy isoflavones genistein and daidzein, modulate the activity of the estrogen receptors (ERs)- and ERß. An additional class of dietary polyphenols that modulate cellular signaling pathways are lignans, compounds that are common constituents of Western diets. In this study, we show that a metabolite of dietary lignans, enterolactone, at physiological concentrations, activates ER-mediated transcription in vitro with preference for ER. The effects of enterolactone are mediated by the ER ligand binding domain and are susceptible to antiestrogen treatment. Furthermore, the affinity of enterolactone toward ER, measured by a novel ligand binding assay, is augmented in cell culture conditions. Moreover, our results demonstrate for the first time that enterolactone has estrogenic activity in vivo. In transgenic estrogen-sensitive reporter mice, enterolactone induces tissue-specific estrogen-responsive reporter gene expression as well as promotes uterine stromal edema and expression of estrogen-responsive endogenous genes (CyclinD1 and Ki67). Taken together, our data show that enterolactone is a selective ER agonist inducing ER-mediated transcription both in vitro in different cell lines and in vivo in the mouse uterus.

This article has been cited by other articles:

				A. M. Kivela, E. Kansanen, H.-K. Jyrkkanen, T. Nurmi, S. Yla-Herttuala, and A.-L. Levonen Enterolactone Induces Heme Oxygenase-1 Expression through Nuclear Factor-E2-Related Factor 2 Activation in Endothelial Cells J. Nutr., July 1, 2008; 138(7): 1263 - 1268. [Abstract] [Full Text] [PDF]