更新于：2024-11-01

ERβ x NR1D1

更新于：2024-11-01

基本信息

关联

项与 ERβ x NR1D1 相关的药物

SR-29065

靶点

ERβ x NR1D1

作用机制

ERβ调节剂 [+1]

在研机构

Chempartner Corp. [+1]

原研机构

Chempartner Corp. [+1]

在研适应症

多发性硬化症

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 ERβ x NR1D1 相关的临床结果

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100 项与 ERβ x NR1D1 相关的转化医学

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0 项与 ERβ x NR1D1 相关的专利（医药）

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项与 ERβ x NR1D1 相关的文献（医药）

2022-08-01·Chemico-Biological Interactions

The effect of 3-Methyl-4-Nitrophenol on the early ovarian follicle development in mice by disrupting the clock genes expression

Article

作者: Fan, Sijie ; Tang, Zeqi ; Sheng, Xia ; Yu, Wenyang ; Yang, Xiaoying ; Zhao, Xinyu ; Xie, Wenqian ; Yuan, Zhengrong ; Han, Yingying ; Zhang, Haolin ; Weng, Qiang ; Chen, Yuan

3-Methyl-4-Nitrophenol (PNMC) is the main degradation product of organophosphate insecticide fenitrothion and a major component of diesel exhaust particles, which is now becoming a widely spread environmental endocrine disruptor. Previous reports showed PNMC exposure can affect the female reproductive system and ovarian function; however, the mechanism remains unclear. The main purpose of this study is to clarify the mechanism underlying the adverse effects of neonatal PNMC treatment on ovarian functions. The neonatal female mice were exposed to 10 mg/kg PNMC and the ovaries were collected on the 7th day after birth. The changes of follicular composition in mice ovaries were analyzed by histological staining, which showed that the proportion of primordial follicles in the ovaries treated by PNMC decreased, while the proportion of secondary follicles increased. The ovarian function was also investigated by detecting the expressions of steroidogenic enzymes (Star, Cyp11a1, Hsd3b1, Cyp17a1, Cyp19a1), gonadotropin receptors (Fshr and Lhr), androgen receptor (Ar), and estrogen receptors (Esr1 and Esr2) by immunohistochemistry or/and real-time quantitative PCR. The expression of Hsd3b1, Cyp17a1 and Esr2 were increased significantly in the PNMC exposed ovaries. Moreover, the expression patterns of clock genes (Bmal1, Clock, Per1, Per2, Cry1, Cry2 and Nr1d1) were disrupted in the ovaries after PNMC exposure. Furthermore, either the expression of DNA Methyltransferase Dnmt3b, or the methylation ratio of CpG islands in the upstream of Cry1 promoter regions were significantly decreased in PNMC exposed ovaries. Altogether, these results indicate that PNMC exposure affects follicle development and ovarian function by interfering with the epigenetic modification and disrupting the expression of clock genes.

2001-01-01·Molecular and Cellular Biology3区 · 生物学

CIA, a Novel Estrogen Receptor Coactivator with a Bifunctional Nuclear Receptor Interacting Determinant

3区 · 生物学

Article

作者: McBroom, Linda D. B. ; Sauvé, Frédéric ; Moraitis, Anna N. ; Giguère, Vincent ; Labrie, Fernand ; Gallant, Josette

ABSTRACT Coregulators for nuclear receptors (NR) are factors that either enhance or repress their transcriptional activity. Both coactivators and corepressors have been shown to use similar but functionally distinct NR interacting determinants containing the core motifs LxxLL and ΦxxΦΦ, respectively. These interactions occur through a hydrophobic cleft located on the surface of the ligand-binding domain (LBD) of the NR and are regulated by ligand-dependent activation function 2 (AF-2). In an effort to identify novel coregulators that function independently of AF-2, we used the LBD of the orphan receptor RVR (which lacks AF-2) as bait in a yeast two-hybrid screen. This strategy led to the cloning of a nuclear protein referred to as CIA (coactivator independent of AF-2 function) that possesses both repressor and activator functions. Strikingly, we observed that CIA not only interacts with RVR and Rev-ErbAα in a ligand-independent manner but can also form complexes with estrogen receptor alpha (ERα) and ERβ in vitro and enhances ERα transcriptional activity in the presence of estradiol (E 2 ). CIA-ERα interactions were found to be independent of AF-2 and enhanced by the antiestrogens EM-652 and ICI 182,780 but not by 4-hydroxytamoxifen and raloxifene. We further demonstrate that CIA-ERα interactions require the presence within CIA of a novel bifunctional NR recognition determinant containing overlapping LxxLL and ΦxxΦΦ motifs. The identification and functional characterization of CIA suggest that hormone binding can create a functional coactivator interaction interface in the absence of AF-2.

Journal of Biosciences

A majority of circadian clock genes are expressed in estrogen receptor and progesterone receptor status-dependent manner in breast cancer

Article

作者: Cacan, Ercan ; Berkel, Caglar

Circadian clocks, biochemical oscillators that are regulated by environmental time cues including the day/night cycle, have a central function in the majority of biological processes. The disruption of the circadian clock can alter breast biology negatively and may promote the development of breast tumors. The expression status of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) were used to classify breast cancer into different molecular subtypes such as triple-negative breast cancer (TNBC). Receptor status-dependent expression of circadian clock genes have been previously studied in breast cancer using relatively small sample sizes in a particular population. Here, using TCGA-BRCA data (n=1119), we found that the expressions of CRY1, PER1, PER2, PER3, BMAL1, CLOCK, RORA, RORB, RORC, NR1D1, NR1D2, and FBXL3 were higher in ER+ breast cancer cells compared with those of ER- status. Similarly, we showed that transcript levels of CRY2, PER1, PER2, PER3, BMAL1, RORA, RORB, RORC, NR1D1, NR1D2, and FBXL3 were higher in PR+ breast cancer cells than in PR- breast cancer cells. We report that the expressions of CRY2, PER1, BMAL1, and RORA were lower, and the expression of NR1D1 was higher, in HER2+ breast cancer cells compared with HER2- breast cancer cells. Moreover, we studied these receptor status-dependent changes in the expressions of circadian clock genes also based on the race and age of breast cancer patients. Lastly, we found that the expressions of CRY2, PER1, PER2, PER3, and CLOCK were higher in non-TNBC than in TNBC, which has the worst prognosis among subtypes. We note that our findings are not always parallel to the observations reported in previous studies with smaller sample sizes performed in different populations and organisms. Our study suggests that receptor status in breast cancer (thus, subtype of breast cancer) might be more important than previously shown in terms of its influence on the expression of circadian clock genes and on the disruption of the circadian clock, and that ER or PR might be important regulators of breast cancer chronobiology that should be taken into account in personalized chronotherapies.