Estrogen receptors do not influence angiogenesis after myocardial infarction.

Background: There is controversy on whether estrogen receptors are present and functioning in the myocardium. Aims. To explore if after myocardial infarction (MI) estrogen receptors α (ERα) and β (ERβ) are upregulated in myocardial tissue and to explore if the presence/ absence of ERα or ERβ influences angiogenesis after MI.

Role of the estrogen/estrogen-receptor-beta axis in the genomic response to pressure overload-induced hypertrophy.

Cardiac hypertrophy, the adaptive response of the heart to overload, is a major risk factor for heart failure and sudden death. Estrogen (E2) and estrogen receptor beta (ERbeta) offer protection against hypertrophy and in the transition to heart failure. However, the underlying pathways remain incompletely defined.

CIDEA interacts with liver X receptors in white fat cells.

Cell death-inducing DNA fragmentation factor alpha-like effector A (CIDEA) is endogenously expressed in human but not rodent white adipocytes. We performed a bioinformatic analysis of the human CIDEA sequence and found conserved amino-acid motifs involved in binding to nuclear receptors. Protein-protein binding experiments and transactivation assays confirmed that CIDEA binds to liver X receptors and regulates their activity in vitro.

Estrogen receptor-beta signals left ventricular hypertrophy sex differences in normotensive deoxycorticosterone acetate-salt mice.

We found earlier that deoxycorticosterone acetate-salt treatment causes blood pressure-independent left ventricular hypertrophy, but only in male mice. To test the hypothesis that the estrogen receptor-β (ERβ) protects the females from left ventricular hypertrophy, we treated male and female ERβ-deficient (ERβ(-/-)) mice and their male and female littermates (wild-type [WT]) with deoxycorticosterone acetate-salt and made them telemetrically normotensive with hydralazine. WT males had increased (+16%) heart weight/tibia length ratios compared with WT females (+7%) at 6 weeks.

Does consuming isoflavones reduce or increase breast cancer risk?

Epidemiological studies suggest that consumption of phytoestrogens, in particular isoflavones, correlates with a lower incidence of breast cancer. However, data from human intervention studies have been less clear. Several meta-analyses have reported beneficial but relatively weak effects of isoflavone consumption on reduction of hot flushes and osteoporosis and improvement of cholesterol levels.

Both liver-X receptor (LXR) isoforms control energy expenditure by regulating brown adipose tissue activity.

Brown adipocytes are multilocular lipid storage cells that play a crucial role in nonshivering thermogenesis. Uncoupling protein 1 (UCP1) is a unique feature of brown fat cells that allows heat generation on sympathetic nervous system stimulation. As conventional transcriptional factors that are activated in various signaling pathways, liver-X receptors (LXRs) play important roles in many physiological processes.

Estrogen signaling via estrogen receptor {beta}.

Estrogens act by binding to and activating two estrogen receptors (ERs), ERα and ERβ. Transcriptional regulation by ERs is controlled by a complex array of factors such as ER-ligand binding, the DNA sequence bound by ERs, ER-interacting cofactors, and chromatin context. This minireview will provide an overview of the most recent advances in the identification of ERβ-regulated target gene networks and ERβ DNA-binding sites.

Decreased fat storage by Lactobacillus paracasei is associated with increased levels of angiopoietin-like 4 protein (ANGPTL4).

Background: Intervention strategies for obesity are global issues that require immediate attention. One approach is to exploit the growing consensus that beneficial gut microbiota could be of use in intervention regimes. Our objective was to determine the mechanism by which the probiotic bacteria Lactobacillus paracasei ssp paracasei F19 (F19) could alter fat storage.

Quantitative proteomics and transcriptomics addressing the estrogen receptor subtype-mediated effects in T47D breast cancer cells exposed to the phytoestrogen genistein.

The present study addresses, by transcriptomics and quantitative stable isotope labeling by amino acids in cell culture (SILAC)-based proteomics, the estrogen receptor α (ERα) and β (ERβ)-mediated effects on gene and protein expression in T47D breast cancer cells exposed to the phytoestrogen genistein. Using the T47D human breast cancer cell line with tetracycline-dependent ERβ expression (T47D-ERβ), the effect of a varying intracellular ERα/ERβ ratio on genistein-induced gene and protein expression was characterized. Results obtained reveal that in ERα-expressing T47D-ERβ cells with inhibited ERβ expression genistein induces transcriptomics and proteomics signatures pointing at rapid cell growth and migration by dynamic activation of cytoskeleton remodeling.

Estrogen-dependent gallbladder carcinogenesis in LXRbeta-/- female mice.

Gallbladder cancer is a highly aggressive disease with poor prognosis that is two to six times more frequent in women than men. The development of gallbladder cancer occurs over a long time (more than 15 y) and evolves from chronic inflammation to dysplasia/metaplasia, carcinoma in situ, and invasive carcinoma. In the present study we found that, in female mice in which the oxysterol receptor liver X receptor-beta (LXRbeta) has been inactivated, preneoplastic lesions of the gallbladder developed and evolved to cancer in old animals.

Estrogen receptors in colorectal cancer: goalkeepers, strikers, or bystanders?

This perspective on Jin et al. (beginning on page 910 in this issue of the journal) discusses the importance of estrogen signaling in colorectal carcinogenesis, with a focus on estrogen receptor beta (ERbeta), which is the predominant ER in the colorectal epithelium. The importance of ERbeta in breast cancer is well described in the literature, and recent studies reveal that ERbeta functions similarly in colorectal cancer.

ERbeta: recent understanding of estrogen signaling.

The discovery of a second estrogen receptor, ERbeta, and the finding that 5alpha-androstane-3beta,17beta-diol (3betaAdiol) strongly binds to ERbeta, have opened up a new aspect of estrogen signaling. Some of the major shifts in our understanding come from finding ERbeta in tissues which do not express ERalpha but are estrogen-responsive; these were called sites of 'indirect estrogen action'. Two key sites that fall into this category are the brain and the prostate.

Estrogen receptor beta decreases survival of p53-defective cancer cells after DNA damage by impairing G₂/M checkpoint signaling.

Estrogen receptor beta (ERβ) inhibits proliferation in different cellular systems by regulating components of the cell cycle machinery. Eukaryotic cells respond to DNA damage by arresting in G₁, S, or G₂ phases of the cell cycle to initiate DNA repair. Most tumor cells due to disruptions in the p53-dependent G₁ pathway are dependent on S-phase and G₂/M checkpoints to maintain genomic integrity in response to DNA damage.

Liver X receptor beta and thyroid hormone receptor alpha in brain cortical layering.

In the past year, two members of the nuclear receptor family, liver X receptor beta (LXRbeta) and thyroid hormone receptor alpha (TRalpha), have been found to be essential for correct migration of neurons in the developing cortex in mouse embryos. TRalpha and LXRbeta bind to identical response elements on DNA and sometimes regulate the same genes. The reason for the migration defect in the LXRbeta(-/-) mouse and the possibility that TRalpha may be involved are the subjects of the present study.

Genome-wide mapping of estrogen receptor-beta-binding regions reveals extensive cross-talk with transcription factor activator protein-1.

Estrogen signaling can occur through a nonclassical pathway involving the interaction of estrogen receptors (ER) with other transcription factors such as activator protein-1 (AP-1) and SP-1. However, there is little mechanistic understanding about this pathway, with conflicting results from in vitro investigations. In this study, we applied the ChIP-on-chip approach to identify ERbeta-binding sites on a genome-wide scale, identifying 1,457 high-confidence binding sites in ERbeta-overexpressing MCF7 breast cancer cells.

The role of estrogen receptor beta (ERbeta) in malignant diseases--a new potential target for antiproliferative drugs in prevention and treatment of cancer.

The discovery of ERbeta in the middle of the 1990s represents a paradigm shift in our understanding of estrogen signaling. It has turned out that estrogen action is not mediated by one receptor, ERalpha, but by two balancing factors, ERalpha and ERbeta, which are often antagonistic to one another. Excitingly, ERbeta has been shown to be widespread in the body and to be involved in a multitude of physiological and pathophysiological events.

ERbeta in CNS: new roles in development and function.

Estrogen acting through two estrogen receptors (ERs), ERalpha and ERbeta, regulates multiple functions in the central nervous system. Studies in rodent brains have revealed that ERalpha is the predominant ER in the hypothalamus and controls reproduction. ERbeta influences on non-reproductive processes and appears to be the main ER subtype expressed in the cerebral cortex, the hippocampus, the cerebellum and the dorsal raphe.

Neuropathologic and biochemical changes during disease progression in liver X receptor beta-/- mice, a model of adult neuron disease.

In amyotrophic lateral sclerosis (ALS), there is selective degeneration of motor neurons that leads to paralysis and death. Although the etiology of ALS is unclear, its heterogeneity suggests that a combination of factors (endogenous and/or environmental) may induce progressive motor neuron stress that results in the activation of different cell death pathways. Alterations of brain cholesterol homeostasis have recently been considered as possible cofactors in many neurodegenerative disorders, including ALS.

Female sex and estrogen receptor-beta attenuate cardiac remodeling and apoptosis in pressure overload.

We investigated sex differences and the role of estrogen receptor-beta (ERbeta) on myocardial hypertrophy in a mouse model of pressure overload. We performed transverse aortic constriction (TAC) or sham surgery in male and female wild-type (WT) and ERbeta knockout (ERbeta(-/-)) mice. All mice were characterized by echocardiography and hemodynamic measurements and were killed 9 wk after surgery.

Proteomics analysis of the estrogen receptor alpha receptosome.

The estrogen receptors (ERs) are ligand-dependent transcription factors that activate transcription by binding to estrogen response elements. Estrogen-mediated effects are tissue- and cell type-specific, determined by the cofactor recruitment to the ERs among other factors. To understand these differences in estrogen action, it is important to identify the various compositions of the ER complexes (ER receptosomes).

Gonadotropin-positive pituitary tumors accompanied by ovarian tumors in aging female ERbeta-/- mice.

At 2 years of age, 100% (23/23) of ERbeta(-/-) female mice have developed large pituitary and ovarian tumors. The pituitary tumors are gonadotropin-positive and the ovarian tumors are sex cord (less differentiated) and granulosa cell tumors (differentiated and estrogen secreting). No male mice had pituitary tumors and no pituitary or ovarian tumors developed in ERalpha(-/-) mice or in ERalphabeta(-/-) double knockout mice.

Levels of 17beta-estradiol receptors expressed in embryonic and adult zebrafish following in vivo treatment of natural or synthetic ligands.

The nuclear receptors encompass a group of regulatory proteins involved in a number of physiological processes. The estrogen receptors (ERs), of which one alpha and one beta form exist in mammals function as transcription factors in response to 17beta-estradiol (E2). In zebrafish there are three gene products of estrogen receptors and they are denoted esr1 (ERalpha), esr2a (ERbeta2) and esr2b (ERbeta1).

GPS2-dependent corepressor/SUMO pathways govern anti-inflammatory actions of LRH-1 and LXRbeta in the hepatic acute phase response.

The orphan receptor LRH-1 and the oxysterol receptors LXRalpha and LXRbeta are established transcriptional regulators of lipid metabolism that appear to control inflammatory processes. Here, we investigate the anti-inflammatory actions of these nuclear receptors in the hepatic acute phase response (APR). We report that selective synthetic agonists induce SUMOylation-dependent recruitment of either LRH-1 or LXR to hepatic APR promoters and prevent the clearance of the N-CoR corepressor complex upon cytokine stimulation.

RBCK1 drives breast cancer cell proliferation by promoting transcription of estrogen receptor alpha and cyclin B1.

Cell cycle regulatory pathways in breast cancer are incompletely described. Here, we report an important role in estrogen receptor alpha (ERalpha)-positive breast cancer cells for the protein kinase C1 (PKC1)-interacting protein RBCK1 in supporting cell cycle progression by driving transcription of ERalpha and cyclin B1. RBCK1-depleted cells exhibited increased accumulation in G(2)-M phase of the cell cycle, decreased proliferation, and reduced mRNA levels for ERalpha and its target genes cyclin D1 and c-myc.

LXRbeta deficient mice have reduced hepatic insulin clearance during hyperinsulinemic euglucemic clamp.

The present study addresses the insulin sensitivity in mice deficient in LXRbeta (LXRbeta(-/-)) as well as in wild type (wt) mice assessed by hyperinsulinemic euglycemic clamp. Wt and LXRbeta(-/-) mice were fed either a normal chow diet or a high fat and high cholesterol diet (HFCD), and insulin sensitivity was assessed by hyperinsulinemic euglycemic clamps. We show that LXRbeta(-/-) mice have reduced insulin clearance during hyperinsulinemic clamps upon feeding both HFCD and a regular chow diet.