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Molecular Endocrinology, doi:10.1210/me.2002-0206
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Molecular Endocrinology 17 (2): 203-208
Copyright © 2003 by The Endocrine Society

Estrogen Receptor (ER)-ß Reduces ER{alpha}-Regulated Gene Transcription, Supporting a "Ying Yang" Relationship between ER{alpha} and ERß in Mice

Marie K. Lindberg, Sofia Movérare, Stanko Skrtic, Hui Gao, Karin Dahlman-Wright, Jan-Åke Gustafsson and Claes Ohlsson

Division of Endocrinology (M.K.L., S.M., S.S., C.O.), Department of Internal Medicine, Sahlgrenska University Hospital, S-41345 Gothenburg, Sweden; and Department of Medical Nutrition and Department of BioSciences (J.-Å.G., H.G., K.D.-W.), Karolinska Institute, Novum, S-14157 Huddinge, Sweden

Address all correspondence and requests for reprints to: Claes Ohlsson, Professor, Department of Internal Medicine, Division of Endocrinology, RCEM, Sahlgrenska University Hospital, S-41345 Gothenburg, Sweden. E-mail: claes.ohlsson{at}medic.gu.se.

Estrogen is of importance for the regulation of adult bone metabolism. The aim of the present study was to determine the role of estrogen receptor-ß (ERß) in vivo on global estrogen-regulated transcriptional activity in bone. The effect of estrogen in bone of ovariectomized mice was determined using microarray analysis including 9400 genes. Most of the genes (95% = 240 genes) that were increased by estrogen in wild-type (WT) mice were also increased by estrogen in ERß-inactivated mice. Interestingly, the average stimulatory effect of estrogen on the mRNA levels of these genes was 85% higher in ERß-inactivated than in WT mice, demonstrating that ERß reduces estrogen receptor-{alpha} (ER{alpha})-regulated gene transcription in bone. The average stimulatory effect of estrogen on estrogen-regulated bone genes in ER{alpha}-inactivated mice was intermediate between that seen in WT and ER{alpha}ß double-inactivated mice. Thus, ERß inhibits ER{alpha}-mediated gene transcription in the presence of ER{alpha}, whereas, in the absence of ER{alpha}, it can partially replace ER{alpha}. In conclusion, our in vivo data indicate that an important physiological role of ERß is to modulate ER{alpha}-mediated gene transcription supporting a "Ying Yang" relationship between ER{alpha} and ERß in mice.

NURSA Molecule Pages Link:

Nuclear Receptors:   ERα  |  ERβ
Ligands:   17β-Estradiol



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