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

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

A genome-wide study of the repressive effects of estrogen receptor beta on estrogen receptor alpha signaling in breast cancer cells

“…Also downregulated genes such as ERa itself (FC 0. by ERa and decrease of S100A6/calcyclin by ERb correlates to the earlier findings of in vivo gene expression in wt and ER knockout mouse bone tissue (Lindberg et al, 2003). Since other array analyses of ERa action have been published previously, we compared our results with another study (Frasor et al, 2003).…”

ERβ in breast cancer—Onlooker, passive player, or active protector?

“…Effects of ERβ-E2 on gene expression were generally lower than ERα-E2 [29]. In breast cancer cells, both ERs stimulate some cell cycle regulation genes such as pS2, TGFα, and p21 Cip1 , but only ERα stimulates c-myc [30].…”

“…Microarray analysis of endogenous gene expression illustrates both common and divergent genes regulated by ERα versus ERβ in the reproductive tissues of mice treated with isoformspecific ligands [27,28], or in bone from ERα (ERKO) and ERβ (BERKO) gene-disrupted mice [29]. Effects of ERβ-E2 on gene expression were generally lower than ERα-E2 [29].…”

Tools to evaluate estrogenic potency of dietary phytoestrogens:A consensus paper from the EU Thematic Network “Phytohealth” (QLKI-2002-2453)

“…This view is further supported by findings in gene array studies in uterus and bone of ERα-KO and ERβ-KO mice. Both studies report that the expression of the vast majority of genes is triggered through the ERα, whereas ERβ has to be regarded as a modulator of the magnitude of the ERα response (Hewitt et al, 2003;Lindberg et al, 2003) The classical in vivo models most commonly used for testing estrogenicity of compounds are summarized in section 5 respective section later. INT INT INT INTAKE OF DIET AKE OF DIET AKE OF DIET AKE OF DIET AKE OF DIETAR AR AR AR ARY Y Y Y Y PHYTOESTROGENS IN EUROPE PHYTOESTROGENS IN EUROPE PHYTOESTROGENS IN EUROPE PHYTOESTROGENS IN EUROPE PHYTOESTROGENS IN EUROPE The limited information on phytoestrogen intake among Europeans has increased during this century (Tables 1 and 2).…”