We have cloned a novel member of the nuclear receptor superfamily. The cDNA clone 29 was isolated from rat prostate library and it encodes protein 485 amino acid residues with calculated molecular weight 54.2 kDa. Clone is unique in that highly homologous to estrogen (ER) protein, particularly DNA-binding domain (95%) C-terminal ligand-binding (55%). Expression tissues investigated by situ hybridization prominent expression found ovary. In expressed epithelial cells secretory alveoli,...

Abstract The rat estrogen receptor (ER) exists as two subtypes, ERα and ERβ, which differ in the C-terminal ligand binding domain N-terminal transactivation domain. In this study we investigated messenger RNA expression of both ER subtypes tissues by RT-PCR compared specificity subtypes. Saturation analysis vitro synthesized human ERβ protein revealed a single component for 16α-iodo-17β-estradiol with high affinity[ dissociation constant (Kd) = 0.1 nm 0.4 protein]. Most estrogenic substances...

The transactivation properties of the two estrogen receptors, ERα and ERβ, were examined with different ligands in context an response element AP1 element. ERβ shown to signal opposite ways when complexed natural hormone estradiol from site: ERα, 17β-estradiol activated transcription, whereas inhibited transcription. Moreover, antiestrogens tamoxifen, raloxifene, Imperial Chemical Industries 164384 potent transcriptional activators at site. Thus, ERs depending on ligand This suggests that...

Estrogens influence the differentiation and maintenance of reproductive tissues affect lipid metabolism bone remodeling. Two estrogen receptors (ERs) have been identified to date, ERα ERβ. We previously generated studied knockout mice lacking receptor α reported severe behavioral phenotypes including complete infertility both male female absence breast tissue development. Here we describe generation β (ERβ −/−) by insertion a neomycin resistance gene into exon 3 coding using homologous...

The estrogen receptor (ER) is a ligand-activated transcription factor that mediates the effects of steroid hormone 17β-estradiol, in both males and females. Since isolation cloning ER, consensus has been only one such exists. finding second subtype ER (ERβ) caused considerable excitement amongst endocrinologists. In this article, we present data regarding genomic structure chromosomal localization human ERβ gene, demonstrating two independent genes do exist human. Furthermore, tissue...

Until recently, only a single type of estrogen receptor (ER) was thought to exist and mediate the genomic effects hormone 17beta-estradiol in mammalian tissues. However, cloning gene encoding second ER, termed ERbeta, from mouse, rat, human has prompted reevaluation signaling system. Based on vitro studies, ERbeta protein binds estradiol with an affinity similar that classical ER (now referred as ERalpha) is able transfected cell lines. Essential further investigations possible physiological...

Peroxisome proliferators such as clofibric acid, nafenopin, and WY-14,643 have been shown to activate PPAR (peroxisome proliferator-activated receptor), a member of the steroid nuclear receptor superfamily. We cloned cDNA from rat that is homologous mouse [Issemann, I. & Green, S. (1990) Nature (London) 347, 645-650], which encodes 97% similar protein with particularly well-conserved putative ligand-binding domain. To search for physiologically occurring activators, we established...

The existence of two rather than one estrogen receptor, today characterized as receptor α (ERα) and β (ERβ), indicates that the mechanism action 17β-estradiol related synthetic drugs is more complex previously thought. Because homology amino acid residues in ligand-binding domain (LBD) ERβ high compared with those ERα LBD, shown to line ligand binding cavity or make direct contacts ligands, it not surprising many ligands have a similar affinity for both subtypes. We report...

The recent discovery that an additional estrogen receptor subtype is present in various rat tissues has advanced our understanding of the mechanisms underlying signaling. Here we report on cloning cDNA encoding mouse homolog receptor-beta (ER beta) and functional characterization ER beta protein. shown to have overlapping DNA-binding specificity with receptor-alpha alpha) activates transcription reporter gene constructs containing estrogen-response elements transient transfections response...

The three-dimensional structure of the DNA-binding domain (DBD) glucocorticoid receptor has been determined by nuclear magnetic resonance spectroscopy and distance geometry. a 71-residue protein fragment containing two "zinc finger" domains is based on large set proton-proton distances derived from Overhauser enhancement spectra, hydrogen bonds in previously identified secondary elements, coordination zinc atoms conserved cysteine residues. DBD found to consist globular body which finger...

Estrogen receptor (ER) β counteracts the activity of ERα in many systems. In agreement with this, we show this study that induced expression ERβ breast cancer cell line T47D reduces 17β-estradiol-stimulated proliferation when mRNA equals ERα. Induction growth exponentially proliferating cells a concomitant decrease components cycle associated proliferation, namely cyclin E, Cdc25A (a key regulator Cdk2), p45 Skp2 p27 Kip1 proteolysis), and an increase Cdk inhibitor . We also observed reduced...

By means of a monoclonal antibody against the rat liver glucocorticoid receptor (GR) in combination with indirect immunoperoxidase technique it has been possible to demonstrate GR-immunoreactive nerve and glial cell nuclei all over tel– diencephalon male rat. Strongly GRimmunoreactive were only present parvocellular part paraventricular hypothalamic nucleus, anterior periventricular ventral mediobasal hypothalamus, CAl CA2 subregion hippocampal formation. Within nucleus substantial overlap...

Many of the effects estrogens on uterus are mediated by ERα, predominant ER in mature organ. Because poor reproductive capacity ERβ knockout (BERKO) female mice (small litter size, multiple-resorbed fetuses), role uterine was explored. In immature uterus, ERα and expressed at comparable levels epithelium stroma, 17β-estradiol (E 2 ) treatment decreases stroma. The untreated BERKO exhibits elevated progesterone receptor (PR) proliferation-associated protein, Ki-67. It also exaggerated...

Blood vessels express estrogen receptors, but their role in cardiovascular physiology is not well understood. We show that vascular smooth muscle cells and blood from receptor beta (ERbeta)-deficient mice exhibit multiple functional abnormalities. In wild-type mouse vessels, attenuates vasoconstriction by an ERbeta-mediated increase inducible nitric oxide synthase expression. contrast, augments ERbeta-deficient mice. Vascular isolated abnormalities of ion channel function. Furthermore,...

We have defined and characterized a region upstream of the bovine prolactin gene that confers repression by glucocorticoids. This 'negative glucocorticoid response element' (nGRE) contains multiple footprinting sites for purified receptor protein between -51 -562 bp. A strong consensus sequence binding within nGRE has not yet been defined, but it is apparent sequences differ from GRE elements confer positive regulation. Unlike 'positive' GREs, enhances promoter activity in absence...

Abstract Estrogen is of importance for the regulation adult bone metabolism. The aim present study was to determine role estrogen receptor-β (ERβ) in vivo on global estrogen-regulated transcriptional activity bone. effect ovariectomized mice determined using microarray analysis including 9400 genes. Most genes (95% = 240 genes) that were increased by wild-type (WT) also ERβ-inactivated mice. Interestingly, average stimulatory mRNA levels these 85% higher than WT mice, demonstrating ERβ...

In normal rats and mice, immunostaining with specific antibodies revealed that nuclei of most prostatic epithelial cells harbor estrogen receptor β (ERβ). rat ventral prostate, 530- 549-aa isoforms the were identified. These sediment in 4S region low-salt sucrose gradients, indicating ERβ does not contain same protein chaperones are associated ERα. Estradiol (E 2 ) binding immunoreactivity coincide on gradient, no indication prostates from mice which gene has been inactivated (BERKO),...