Implications of estrogen receptor alpha and estrogen receptor beta for adipose tissue functions and cardiometabolic complications

2013 ◽  
Vol 15 (3) ◽  
Author(s):  
Hui Gao ◽  
Karin Dahlman-Wright
Keyword(s):  
Estrogen Receptor ◽  
Adipose Tissue ◽  
Estrogen Receptor Alpha ◽  
Molecular Mechanisms ◽  
Estrogen Receptor Beta ◽  
Estrogen Receptor Α ◽  
Endocrine Function ◽  
Estrogen Signaling ◽  
Strongly Connected

AbstractThere is growing evidence that estrogen signaling regulates energy metabolism and exerts important functions in maintaining adipose tissue metabolism, including controlling the distribution of body fat. Changes in the physiological functions of adipose tissue, particularly the white adipose tissue, have been strongly connected to obesity and the development of related cardiometabolic complications. In this review, we will focus on discussing the role of estrogen signaling in regulating adipocyte differentiation, metabolism and its endocrine function with a focus on the possible underlying molecular mechanisms mediated by estrogen receptor α and estrogen receptor β.

Membrane estrogen receptor α is essential for estrogen signaling in the male skeleton

2018 ◽  
Vol 239 (3) ◽  
pp. 303-312 ◽  
Author(s):  
H H Farman ◽  
K L Gustafsson ◽  
P Henning ◽  
L Grahnemo ◽  
V Lionikaite ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Estrogen Receptor Α ◽  
Estrogen Signaling ◽  
Areal Bone Mineral Density ◽  
Male Mice ◽  
Mineral Density ◽  
Intact Male ◽  
Trabecular Thickness ◽  
Total Body

The importance of estrogen receptor α (ERα) for the regulation of bone mass in males is well established. ERα mediates estrogenic effects both via nuclear and membrane-initiated ERα (mERα) signaling. The role of mERα signaling for the effects of estrogen on bone in male mice is unknown. To investigate the role of mERα signaling, we have used mice (Nuclear-Only-ER; NOER) with a point mutation (C451A), which results in inhibited trafficking of ERα to the plasma membrane. Gonadal-intact male NOER mice had a significantly decreased total body areal bone mineral density (aBMD) compared to WT littermates at 3, 6 and 9 months of age as measured by dual-energy X-ray absorptiometry (DEXA). High-resolution microcomputed tomography (µCT) analysis of tibia in 3-month-old males demonstrated a decrease in cortical and trabecular thickness in NOER mice compared to WT littermates. As expected, estradiol (E2) treatment of orchidectomized (ORX) WT mice increased total body aBMD, trabecular BV/TV and cortical thickness in tibia compared to placebo treatment. E2 treatment increased these skeletal parameters also in ORX NOER mice. However, the estrogenic responses were significantly decreased in ORX NOER mice compared with ORX WT mice. In conclusion, mERα is essential for normal estrogen signaling in both trabecular and cortical bone in male mice. Increased knowledge of estrogen signaling mechanisms in the regulation of the male skeleton may aid in the development of new treatment options for male osteoporosis.

scholarly journals Regulatory Interplay between miR-181a-5p and Estrogen Receptor Signaling Cascade in Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 543
Author(s):  
Rosaria Benedetti ◽  
Chiara Papulino ◽  
Giulia Sgueglia ◽  
Ugo Chianese ◽  
Tommaso De Marchi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Endocrine Therapy ◽  
Mirna Expression ◽  
Estrogen Receptor Alpha ◽  
Estrogen Signaling ◽  
Integrated Analysis ◽  
Tumor Resistance ◽  
Estrogen Receptor Signaling

The efficacy and side effects of endocrine therapy in breast cancer (BC) depend largely on estrogen receptor alpha (ERα) expression, the specific drug administered, and treatment scheduling. Although the benefits of endocrine therapy outweigh any adverse effects in the initial stages of BC, later- or advanced-stage tumors acquire resistance to treatments. The mechanisms underlying tumor resistance to therapy are still not well understood, posing a major challenge for BC patient care. Epigenetic regulation and miRNA expression may be involved in the switch from a treatment-sensitive to a treatment-resistant state and could provide a valid therapeutic strategy for ERα negative BC. Here, a hybrid lysine-specific histone demethylase inhibitor, MC3324, displaying selective estrogen receptor down-regulator-like activities in BC, was used to highlight the interplay between epigenetic and ERα signaling. MC3324 anticancer action is mediated by microRNA (miRNA) expression regulation, indicating an innovative function for this molecule. Integrated analysis suggests a crosstalk between estrogen signaling, ERα interactors, miRNAs, and their putative targets. Specifically, miR-181a-5p expression is regulated by MC3324 and has an impact on cellular levels of ERα. A comparison of breast tumor versus healthy mammary tissues confirmed the important role of miR-181a-5p in ERα regulation and points to its putative predictive function in BC therapy.

scholarly journals Expression of Estrogen Receptor Alpha and Evaluation of Histological Degeneration Scores in Fibroblasts of Hypertrophied Ligamentum Flavum: A Qualitative Study

Biomolecules ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1752
Author(s):  
Christina C. Westhoff ◽  
Christian-Dominik Peterlein ◽  
Hanna Daniel ◽  
Juergen R. Paletta ◽  
Roland Moll ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Estrogen Receptor Alpha ◽  
Ligamentum Flavum ◽  
Estrogen Receptor Α ◽  
Group Differences ◽  
Elastic Fibers ◽  
Disk Herniation ◽  
Spinal Decompression ◽  
Lumbar Spinal

The most common spinal disorder in elderly is lumbar spinal stenosis (LSS), resulting partly from ligamentum flavum (LF) hypertrophy. Its pathophysiology is not completely understood. The present study wants to elucidate the role of estrogen receptor α (ER α) in fibroblasts of hypertrophied LF. LF samples of 38 patients with LSS were obtained during spinal decompression. Twelve LF samples from patients with disk herniation served as controls. Hematoxylin & Eosin (H&E) and Elastica stains and immunohistochemistry for ER α were performed. The proportions of fibrosis, loss and/or degeneration of elastic fibers and proliferation of collagen fibers were assessed according to the scores of Sairyo and Okuda. Group differences in the ER α and Sairyo and Okuda scores between patients and controls, male and female sex and absence and presence of additional orthopedic diagnoses were assessed with the Mann–Whitney U test. There was a tendency towards higher expression of ER α in LF fibroblasts in the hypertrophy group (p = 0.065). The Sairyo and Okuda scores were more severe for the hypertrophy group but, in general, not statistically relevant. There was no statistically relevant correlation between the expression of ER α and sex (p = 0.326). ER α expression was higher in patients with osteochondrosis but not statistically significant (p = 0.113). In patients with scoliosis, ER α expression was significantly lower (p = 0.044). LF hypertrophy may be accompanied by a higher expression of ER α in fibroblasts. No difference in ER α expression was observed regarding sex. Further studies are needed to clarify the biological and clinical significance of these findings.

scholarly journals miR-22 Inhibits Estrogen Signaling by Directly Targeting the Estrogen Receptor α mRNA

2009 ◽  
Vol 29 (13) ◽  
pp. 3783-3790 ◽  
Author(s):  
Deo Prakash Pandey ◽  
Didier Picard
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Breast Cancer Cells ◽  
Estrogen Receptor Α ◽  
Estrogen Signaling ◽  
Systematic Assessment ◽  
Small Noncoding Rnas ◽  
Evolutionarily Conserved ◽  
Target Sites

ABSTRACT Estrogen receptor α (ERα) is a ligand-regulated transcription factor with a broad range of physiological functions and one of the most important classifiers in breast cancer. MicroRNAs (miRNAs) are small noncoding RNAs that have emerged as important regulators of gene expression in a plethora of physiological and pathological processes. Upon binding the 3′ untranslated region (UTR) of target mRNAs, miRNAs typically reduce their stability and/or translation. The ERα mRNA has a long 3′ UTR of about 4.3 kb which has been reported to reduce mRNA stability and which bears evolutionarily conserved miRNA target sites, suggesting that it might be regulated by miRNAs. We have performed a comprehensive and systematic assessment of the regulatory role of all miRNAs that are predicted to target the 3′ UTR of the ERα mRNA. We found that miR-22 represses ERα expression most strongly and by directly targeting the ERα mRNA 3′ UTR. Of the three predicted miR-22 target sites in the 3′ UTR, the evolutionarily conserved one is the primary target. miR-22 overexpression leads to a reduction of ERα levels, at least in part by inducing mRNA degradation, and compromises estrogen signaling, as exemplified by its inhibitory impact on the ERα-dependent proliferation of breast cancer cells.

scholarly journals Estrogen receptor beta in prostate cancer: friend or foe?

2014 ◽  
Vol 21 (4) ◽  
pp. T219-T234 ◽  
Author(s):  
Adam W Nelson ◽  
Wayne D Tilley ◽  
David E Neal ◽  
Jason S Carroll
Keyword(s):  
Prostate Cancer ◽  
Estrogen Receptor ◽  
Animal Studies ◽  
Estrogen Receptor Alpha ◽  
Estrogen Receptor Beta ◽  
Cancer Cell Line ◽  
Future Research ◽  
Prostate Carcinogenesis ◽  
Receptor Beta

Prostate cancer is the commonest, non-cutaneous cancer in men. At present, there is no cure for the advanced, castration-resistant form of the disease. Estrogen has been shown to be important in prostate carcinogenesis, with evidence resulting from epidemiological, cancer cell line, human tissue and animal studies. The prostate expresses both estrogen receptor alpha (ERA) and estrogen receptor beta (ERB). Most evidence suggests that ERA mediates the harmful effects of estrogen in the prostate, whereas ERB is tumour suppressive, but trials of ERB-selective agents have not translated into improved clinical outcomes. The role of ERB in the prostate remains unclear and there is increasing evidence that isoforms of ERB may be oncogenic. Detailed study of ERB and ERB isoforms in the prostate is required to establish their cell-specific roles, in order to determine if therapies can be directed towards ERB-dependent pathways. In this review, we summarise evidence on the role of ERB in prostate cancer and highlight areas for future research.

The role of estrogen and estrogen receptor-α in male adipose tissue

2001 ◽  
Vol 178 (1-2) ◽  
pp. 147-154 ◽  
Author(s):  
Paul S Cooke ◽  
Patricia A Heine ◽  
Julia A Taylor ◽  
Dennis B Lubahn
Keyword(s):  
Estrogen Receptor ◽  
Adipose Tissue ◽  
Estrogen Receptor Α

scholarly journals Role of Estrogen Receptor Signaling in Breast Cancer Metastasis

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Sudipa Saha Roy ◽  
Ratna K. Vadlamudi
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Breast Cancer Cells ◽  
Molecular Mechanisms ◽  
Cancer Metastasis ◽  
Metastatic Breast ◽  
Estrogen Signaling

Metastatic breast cancer is a life-threatening stage of cancer and is the leading cause of death in advanced breast cancer patients. Estrogen signaling and the estrogen receptor (ER) are implicated in breast cancer progression, and the majority of the human breast cancers start out as estrogen dependent. Accumulating evidence suggests that ER signaling is complex, involving coregulatory proteins and extranuclear actions. ER-coregualtory proteins are tightly regulated under normal conditions with miss expression primarily reported in cancer. Deregulation of ER coregualtors or ER extranuclear signaling has potential to promote metastasis in ER-positive breast cancer cells. This review summarizes the emerging role of ER signaling in promoting metastasis of breast cancer cells, discusses the molecular mechanisms by which ER signaling contributes to metastasis, and explores possible therapeutic targets to block ER-driven metastasis.

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