Estrogen Receptor (ER)-β Reduces ERα-Regulated Gene Transcription, Supporting a “Ying Yang” Relationship between ERα and ERβ in Mice

The Endocrine Society - Tập 17 Số 2 - Trang 203-208 - 2003
Marie K. Lagerquist1, Sofia Movérare1, Stanko Skrtic1, Hui Gao2, Karin Dahlman‐Wright2, Jan-Ακε Gustafsson2, Claes Ohlsson1
1Division of Endocrinology (M.K.L., S.M., S.S., C.O.), Department of Internal Medicine, Sahlgrenska University Hospital, S-41345 Gothenburg, Sweden
2Department of Medical Nutrition and Department of BioSciences (J.-Å.G., H.G., K.D.-W.), Karolinska Institute, Novum, S-14157 Huddinge, Sweden

Tóm tắt

Abstract 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-β (ERβ) 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 ERβ-inactivated mice. Interestingly, the average stimulatory effect of estrogen on the mRNA levels of these genes was 85% higher in ERβ-inactivated than in WT mice, demonstrating that ERβ reduces estrogen receptor-α (ERα)-regulated gene transcription in bone. The average stimulatory effect of estrogen on estrogen-regulated bone genes in ERα-inactivated mice was intermediate between that seen in WT and ERαβ double-inactivated mice. Thus, ERβ inhibits ERα-mediated gene transcription in the presence of ERα, whereas, in the absence of ERα, it can partially replace ERα. In conclusion, our in vivo data indicate that an important physiological role of ERβ is to modulate ERα-mediated gene transcription supporting a “Ying Yang” relationship between ERα and ERβ in mice.

Từ khóa


Tài liệu tham khảo

Sims, 2000, In vivo analysis of male and female estrogen receptor α, β and double knockouts reveals a dual role for ERβ in bone remodelling., J Bone Miner Res, 15, 1088

Windahl, 1999, Increased cortical bone mineral content but unchanged trabecular bone mineral density in female ERβ(−/−) mice., J Clin Invest, 104, 895, 10.1172/JCI6730

Windahl, 2001, Female estrogen receptor β−/− mice are partially protected against age-related trabecular bone loss., J Bone Miner Res, 16, 1388, 10.1359/jbmr.2001.16.8.1388

Pettersson, 1997, Mouse estrogen receptor β forms estrogen response element-binding heterodimers with estrogen receptor α., Mol Endocrinol, 11, 1486

Pettersson, 2000, Estrogen receptor β acts as a dominant regulator of estrogen signaling., Oncogene, 19, 4970, 10.1038/sj.onc.1203828

Hall, 1999, The estrogen receptor β-isoform (ERβ) of the human estrogen receptor modulates ERα transcriptional activity and is a key regulator of the cellular response to estrogens and antiestrogens., Endocrinology, 140, 5566, 10.1210/endo.140.12.7179

Paech, 1997, Differential ligand activation of estrogen receptors ERα and ERβ at AP1 sites., Science, 277, 1508, 10.1126/science.277.5331.1508

Weihua, 2000, Estrogen receptor (ER)β, a modulator of ERα in the uterus., Proc Natl Acad Sci USA, 97, 5936, 10.1073/pnas.97.11.5936

Weihua, 2001, A role for estrogen receptor β in the regulation of growth of the ventral prostate., Proc Natl Acad Sci USA, 98, 6330, 10.1073/pnas.111150898

Pendaries, 2002, The AF-1 activation-function of ERα may be dispensable to mediate the effect of estradiol on endothelial NO production in mice., Proc Natl Acad Sci USA, 99, 2205, 10.1073/pnas.042688499

Lindberg, 2002, Estrogen receptor specificity for the effects of estrogen in ovariectomized mice., J Endocrinol, 174, 167, 10.1677/joe.0.1740167

Nemere, 1998, Membrane receptors for steroid hormones: a case for specific cell surface binding sites for vitamin D metabolites and estrogens., Biochem Biophys Res Commun, 248, 443, 10.1006/bbrc.1998.8492

Le Mellay, 1999, Gα(q/11) and gβγ proteins and membrane signaling of calcitriol and estradiol., J Cell Biochem, 75, 138, 10.1002/(SICI)1097-4644(19991001)75:1<138::AID-JCB14>3.0.CO;2-I

Kousteni, 2001, Nongenotropic, sex-nonspecific signaling through the estrogen or androgen receptors: dissociation from transcriptional activity., Cell, 104, 719

Giangrande, 1997, Mapping and characterization of the functional domains responsible for the differential activity of the A and B isoforms of the human progesterone receptor., J Biol Chem, 272, 32889, 10.1074/jbc.272.52.32889

Oakley, 1996, The human glucocorticoid receptor β isoform. Expression, biochemical properties, and putative function., J Biol Chem, 271, 9550, 10.1074/jbc.271.16.9550

Vegeto, 1993, Human progesterone receptor A form is a cell- and promoter-specific repressor of human progesterone receptor B function., Mol Endocrinol, 7, 1244

Omoto, 2001, Expression, function, and clinical implications of the estrogen receptor β in human lung cancers., Biochem Biophys Res Commun, 285, 340, 10.1006/bbrc.2001.5158

Lindberg, 2001, Estrogen receptor specificity in the regulation of the skeleton in female mice., J Endocrinol, 171, 229, 10.1677/joe.0.1710229

Krege, 1998, Generation and reproductive phenotypes of mice lacking estrogen receptor β., Proc Natl Acad Sci USA, 95, 15677, 10.1073/pnas.95.26.15677

Lubahn, 1993, Alteration of reproductive function but not prenatal sexual development after insertional disruption of the mouse estrogen receptor gene., Proc Natl Acad Sci USA, 90, 11162, 10.1073/pnas.90.23.11162

Vidal, 2000, Estrogen receptor specificity in the regulation of skeletal growth and maturation in male mice., Proc Natl Acad Sci USA, 97, 5474, 10.1073/pnas.97.10.5474

Chomczynski, 1987, Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction., Anal Biochem, 162, 156, 10.1016/0003-2697(87)90021-2

Thông tin
Thông tin xuất bản

The Endocrine Society

Tập 17 Số 2

203-208

Thông tin tác giả