Tissue Distribution and Quantitative Analysis of Estrogen Receptor-α (ERα) and Estrogen Receptor-β (ERβ) Messenger Ribonucleic Acid in the Wild-Type and ERα-Knockout Mouse

Abstract

Until recently, only a single type of estrogen receptor (ER) was thought to exist and mediate the genomic effects of the hormone 17beta-estradiol in mammalian tissues. However, the cloning of a gene encoding a second type of ER, termed ERbeta, from the mouse, rat, and human has prompted a reevaluation of the estrogen signaling system. Based on in vitro studies, the ERbeta protein binds estradiol with an affinity similar to that of the classical ER (now referred to as ERalpha) and is able to mediate the effects of estradiol in transfected mammalian cell lines. Essential to further investigations of the possible physiological roles of ERbeta, and its possible interactions with ERalpha, are data on the tissue distribution of the two ER types. Herein, we have described the optimization and use of an RNase protection assay able to detect and distinguish messenger RNA (mRNA) transcripts from both the ERalpha and ERbeta genes in the mouse. Because this assay is directly quantitative, a comparison of the levels of expression within various tissues was possible. In addition, the effect of disruption of the ERalpha gene on the expression of the ERbeta gene was also investigated using the ERalpha-knockout (ERKO) mouse. Transcripts encoding ERalpha were detected in all the wild-type tissues assayed from both sexes. In the female reproductive tract, the highest expression of ERbeta mRNA was observed in the ovary and showed great variation among individual animals; detectable levels were observed in the uterus and oviduct, whereas mammary tissue was negative. In the male reproductive tract, significant expression of ERbeta was seen in the prostate and epididymis, whereas the testes were negative. In other tissues of both sexes, the hypothalamus and lung were clearly positive for both ERalpha and ERbeta mRNA. The ERKO mice demonstrated slightly reduced levels of ERbeta mRNA in the ovary, prostate, and epididymis. These data, in combination with the several described phenotypes in both sexes of the ERKO mouse, suggest that the biological functions of the ERbeta protein may be dependent on the presence of ERalpha in certain cell types and tissues. Further characterization of the physiological phenotypes in the ERKO mice may elucidate possible ERbeta specific actions.

Role of estrogen receptor β in uterine stroma and epithelium: Insights from estrogen receptor β −/− mice

“…It is currently thought that in the uterus, stromal ER␣ induces secretion of EGF. Although ER␣ is the predominant ER in the adult rodent uterus, ER␤ mRNA has also been detected in WT and ER␣ Ϫ/Ϫ mouse uteri (11). Targeted disruption of ER␤ in mice (12) has revealed roles for ER␤ in differentiation of various epithelial and nonepithelial cell types in many tissues and organs (13)(14)(15)(16)(17)(18)(19).…”

Impact of the nuclear receptor coactivator AIB1 isoform AIB1-Δ3 on estrogenic ligands with different intrinsic activity

“…Effects of AIB1-D3 on the activation of ER-b ER-b is widely expressed in normal and malignant tissues (Couse et al, 1997;Kuiper et al, 1997;Roger et al, 2001), but the tissue distribution differs from ERa (Nilsson and Gustafsson, 2002). Through ER-b, 17b-estradiol can regulate different sets of genes (Couse et al, 1997) and can oppose the effect of ER-a (Hall and McDonnell, 1999).…”

“…Through ER-b, 17b-estradiol can regulate different sets of genes (Couse et al, 1997) and can oppose the effect of ER-a (Hall and McDonnell, 1999). We therefore examined whether AIB1 and AIB1-D3 can act as coactivators for ER-b.…”

“…The discovery of a second ER gene (ER-b), which has a different tissue distribution relative to ER-a, has gone some way to explaining tissue-specific effects (Couse et al, 1997;Kuiper et al, 1997). In addition, the recently discovered tissue-specific nuclear receptor coactivators and corepressors, which can modify the transcriptional activity of the ER and other nuclear receptors, also play a role in SERM activity (McKenna et al, 1999).…”

Organizational and activational effects of estrogenic endocrine disrupting chemicals

“…Both ERα and ERβ are represented in the vagina and central nervous system (Couse et al, 1997;Osterlund et al, 2000;Shugrue et al, 1997). Despite the importance of the brain and vagina as estrogen target tissues, relatively little is known about the role of these two estrogen receptor isoforms, ERα and ERβ, during development of these tissues (Osterlund et al, 2000;Shugrue et al, 1997).…”