Disease relevance of Esr1

• In this experimental study, we compared the effects of the selective estrogen-receptor (ER) beta agonist biochanin A, and the selective ERalpha agonist ethinylestradiol, on the development of intimal hyperplasia after balloon injury and on uterus morphology [1].
• The ER-mediated repression of the PR immunoreactivity was evidently restricted to the uterine epithelium, as we found that in the epithelial cells of the mammary gland and in cells of N-nitrosomethylurea-induced mammary carcinomas the PR expression was induced by estrogens and was blocked by the pure antiestrogen ZM 182780 [2].
• The inhibitory effect of estradiol on food intake and body weight was blocked by co-administration of ER-beta antisense ODN, whereas ER-alpha antisense ODN did not show any influence [3].
• CONCLUSIONS: These findings collectively suggest that, in addition to blockade of androgen receptors, flutamide-mediated ER upregulation is likely to play a role in mediating the salutary effect of flutamide on cardiac function after trauma hemorrhage [4].
• Estrogen receptor expression in lumbosacral dorsal root ganglion cells innervating the female rat urinary bladder [5].

Psychiatry related information on Esr1

• Water deprivation eliminated ER-beta-immunoreactivity (-ir) in SON and magnocellular PVN of sham-lesioned animals [6].
• Alcohol abuse appears to induce an increase in ER content of human liver, especially in patients with alcoholic hepatitis actively drinking [7].
• Fadrozole treatment resulted in a 59% decrease in brain nuclear estrogen receptor occupation relative to the T group [8].
• Hormonal priming and triggering of maternal behavior in the rat with special reference to the relations between estrogen receptor binding and ER mRNA in specific brain regions [9].
• Impact of the selective estrogen receptor modulator, tamoxifen, on neuronal outgrowth and survival following toxic insults associated with aging and Alzheimer's disease [10].

High impact information on Esr1

• Experimental results indicate that positive and negative transcriptional effects of estrogen receptor are mediated by separate functional domains, and suggest the protein-protein interactions between steroid hormone receptors and other transcription factor(s) mediate inhibition [11].
• Mutational analysis of estrogen receptor confirms that inhibition is a function of receptor, and that transcriptional activation and inhibition require distinct, separable structural elements [11].
• We propose that the T3 receptor binds to estrogen response elements in a transcriptionally inactive form and competes for estrogen receptor binding, resulting in a net decrease in gene expression [12].
• We believe that the estradiol receptor exerts its effect by binding to a small number of high affinity sites on the genome, while also having a finite low affinity for nonspecific DNA sequences [13].
• The interaction of estradiol-receptor protein with the genome: an argument for the existence of undetected specific sites [13].

Chemical compound and disease context of Esr1

• These data, which are considered hypothesis generating, provide evidence that low doses of vorozole in the diet select for mammary carcinomas with an increased ER positive phenotype [14].
• Functionality of estrogen receptor and tamoxifen treatment of R3327 Dunning rat prostate adenocarcinoma [15].
• Biological characteristics and estrogen (ER) and progesterone (PR) receptors were studied in male mammary carcinomas induced by 7,12-dimethylbenz(a)anthracene (DMBA) in male inbred Sprague-Dawley rats (MM) [16].
• The selective estrogen receptor modulator trioxifene (LY133314) inhibits metastasis and extends survival in the PAIII rat prostatic carcinoma model [17].
• The use of decapitation after either ether or ketamine anesthesia is appropriate for measuring ER and PR receptors in rat uteri [18].

Biological context of Esr1

• Using PEETA (Primer extension, Electrophoresis, Elution, Tailing, and Amplification), we established that all Esr1 leader exons, previously identified in other organs, such as the uterus and pituitary, were transcribed in the gubernaculum, with the major form being O/B [19].
• The RNA protection assays, RT-PCR, and Western blot experiments revealed that isoform-specific mRNA transcripts generated by alternative splicing of the C-leader sequence on coding exons 1 and 2 of the Esr1 gene gave the 46- and 66-kDa ESR1 proteins [19].
• Striking sex difference was detected in the expression of estrogen receptor (ER) beta mRNA and protein by nonisotopic in situ hybridization and immunohistochemistry in the anteroventral periventricular nucleus (AVPV) of the rat preoptic area [20].
• These results indicate that phosphorylation and synthesis of some regulatory factor(s) other than or in addition to the estrogen receptor (ER) are essential for transactivation of the PR gene [21].
• Deletion of the cyclic AMP/Ca2+ response element (CRE/CaRE) nearly abolished E2-triggered responses with either ER [22].

Anatomical context of Esr1

• Using electrophoretic mobility shift assays, the consensus ERE was shown to bind ERbeta, the predominant subtype present in rat granulosa cells, and ERalpha, the predominant subtype present in luteal cells, whereas the putative ERE-like region (ERE3) of the proximal PR promoter did not bind either ER subtype [21].
• In addition to the corpus luteum, PRL-induced ER expression might provide a mechanism for fine-tuning the responsiveness of other target tissues, such as the decidua and mammary gland, to these two hormones [23].
• In tissues of the nervous system, including frontal cortex, hippocampus, and hypothalamus, ER beta1 was present in a 2- to 6-fold greater abundance than ER beta2 [24].
• ER alpha protein exhibited a differential distribution in the ovary with no detectable expression in the granulosa cells but evidence of ER alpha IR in germinal epithelium, interstitial cells, and thecal cells [25].
• Importantly, ER beta messenger RNA (mRNA) was localized to rat prostatic epithelial cells, which contrasts with the stromal localization of ER alpha in the rat prostate [26].

Associations of Esr1 with chemical compounds

• Accordingly, estrogen regulation in cells from neonatal hearts, as reported in several studies, may not correspond to that occurring in fully differentiated adult hearts, because of an altered degree of ER expression [27].
• Treatments of rats with testosterone (T) plus estradiol-17beta (E2) (T+E2) or T alone induced no discernible alterations in ER alpha, ER beta, and PR mRNA levels in the VP, DP and LP, while those with E2 caused a general decline in the expression of all three transcripts [28].
• Expression of estrogen receptor-alpha and cFos in norepinephrine and epinephrine neurons of young and middle-aged rats during the steroid-induced luteinizing hormone surge [29].
• For example, genistein competed effectively for estradiol binding to ER beta1 but was > 150-fold weaker at competing from ER beta2 [24].
• In the oviduct and uterus, IR for ER alpha, but not ER beta, was found in luminal epithelium, stromal cells, muscle cells, and gland cells [25].
• Although both PPT and DPN decreased hepatic injury following trauma-hemorrhage, ER-alpha agonist PPT appears to be more effective in downregulating NF-kappaB and AP-1 activity, and iNOS induction [30].

Physical interactions of Esr1

• ER beta2 bound estradiol with a lower affinity (Kd 5.1 nM) than either ER alpha (0.19 nM) or ER beta1 (0.14 nM) [24].
• Interestingly, this slow and gradual transcription rate increase of the endogenous PR gene did not parallel binding of E2 to ER, which was maximized within 30 min [31].
• The results demonstrate that labeled estrogen receptor can bind to Pit-1 immobilized on glutathione agarose beads [32].
• Estrogen receptor alpha forms estrogen-dependent multimolecular complexes with insulin-like growth factor receptor and phosphatidylinositol 3-kinase in the adult rat brain [33].
• However, TERP-1 may compete with ER for binding sites of receptor cofactors because steroid receptor coactivator-1 (SRC-1) rescued the inhibitory actions of TERP-1 [34].

Co-localisations of Esr1

• Progesterone receptor (PR) messenger RNA (mRNA) is concentrated in neurons of the preoptic area and other regions of the rat hypothalamus where it is colocalized with the estrogen receptor and regulated by changes in the steroid hormonal milieu [35].

Regulatory relationships of Esr1

• Estrogen receptor beta (ER beta) mRNA is expressed in several rat brain regions where ER alpha is abundant [36].
• Thus, TH is transcriptionally regulated by estradiol in opposite directions depending on ER subtype [22].
• The ER and IGF-I receptor antagonists similarly blocked the E(2)-induced increase in neurite lengths in ER alpha-transfected cells [37].
• Within the infralimbic, agranular insular, primary motor, parietal association, perirhinal, and lateral entorhinal cortices, an average of 95.6% +/- 0.8% (intact) and 94.5% +/- 1.4% (ovx) of all ER-beta-immunoreactive cells coexpress parvalbumin, and this proportion is strikingly similar across these diverse cortical regions [38].
• Together, these results indicated that membrane ER-mediated E2 inhibition of the TX-stimulated LHRH self-priming pathway involves a blockade of gonadotrope PR phosphorylation/activation, but not a deficient response of PR to phosphorylases [39].

Other interactions of Esr1

• Cotransfection of ER beta2 had no effect on ER beta1 activation when used in a equal ratio [24].
• Mapping the TH promoter showed that the putative half estrogen response element (ERE) motif at - 675, as well as the activation protein 1 motif at - 205, were not required for response to E2 with either ER [22].
• Estrogen receptor-beta, but not estrogen receptor-alpha, is expressed in prolactin neurons of the female rat paraventricular and supraoptic nuclei: comparison with other neuropeptides [40].
• Caveolin-1 was also shown to be present in isolated CNS myelin and oligodendrocyte plasma membranes, where it was partially colocalized with ER [41].
• Nuclear ER-alpha ir was found in a population of thyrotropin-releasing hormone (TRH)-expressing neurons in the PVN (5.93% +/- 1.20% SEM), but not in any other identified cell phenotype of the PVN and SON [40].

Analytical, diagnostic and therapeutic context of Esr1

• Previous immunocytochemical (ICC) and in situ hybridization (ISH) studies detected either low levels or absence of the classical estrogen receptor (ER-alpha) in the PVN and the SON of the rat [42].
• We demonstrated by semiquantitative RT-PCR and RNase protection that ER beta2 mRNA was expressed at levels equal to those of the previously published ER beta (ER beta1) in ovary, prostate, pituitary, and muscle [24].
• Double-label immunofluorescence revealed that 66% of ER beta-ir cells coexpressed ER alpha in the caudal VMH of the P5 female rat [43].
• Immunohistochemical analysis showed a significant down-regulation of estrogen receptor-alpha (ERalpha) in uterine epithelium after 17beta-estradiol treatment, but not after treatment with the SSE; no significant differences among groups were observed in ER-alpha uterine stromal levels [44].
• At the onset of resuscitation, rats received vehicle, flutamide (25 mg/kg body wt), flutamide in combination with estrogen receptor (ER) antagonist ICI-182,780 (3 mg/kg body wt), or ICI-182,780 alone [45].

References