Esr2, also known as estrogen receptor β, is a nuclear estrogen receptor. Estrogens, along with their receptors including Esr2, play crucial roles in regulating male reproductive and non-reproductive organs, as well as female physiological processes. In the body, Esr2 is involved in various pathways such as those related to lipid and glucose metabolism in adipose tissue, and may be associated with estrogen-mediated genomic mechanisms regulating genes like Slc2a4 [3,4,5].

In terms of disease-related findings, Esr2 polymorphisms show different associations with cancer risks. For example, the rs1256049 polymorphism in the Esr2 gene is associated with a higher risk of prostate cancer in the Caucasian population and a lower risk in the Asian population, while rs4986938 is not associated with prostate cancer risk. In breast cancer, the rs1256030 variant of the Esr2 gene and haplotype GAT were associated with susceptibility as risk factors in a Mexican population sample [1,6]. Also, in knee osteoarthritis, lipoxin A4 can inhibit fibroblast-like synoviocytes ferroptosis by activating the Esr2/LPAR3/Nrf2 axis, alleviating pain and pathological progression [2].

In conclusion, Esr2 is essential in multiple physiological and pathological processes. Through studies on gene polymorphisms and animal models in diseases like cancer and osteoarthritis, we've gained insights into its role. Understanding Esr2-mediated mechanisms provides potential targets for disease treatment, especially in areas where estrogen-related signaling is disrupted.

References:

1. Chang, Xueliang, Wang, Hu, Yang, Zhan, Li, Jingdong, Han, Zhenwei. . ESR2 polymorphisms on prostate cancer risk: A systematic review and meta-analysis. In Medicine, 102, e33937. doi:10.1097/MD.0000000000033937. https://pubmed.ncbi.nlm.nih.gov/37335680/

2. Hu, Zhehan, Chen, Liang, Zhao, Jihui, Shen, Peng, Yang, Yue. 2024. Lipoxin A4 ameliorates knee osteoarthritis progression in rats by antagonizing ferroptosis through activation of the ESR2/LPAR3/Nrf2 axis in synovial fibroblast-like synoviocytes. In Redox biology, 73, 103143. doi:10.1016/j.redox.2024.103143. https://pubmed.ncbi.nlm.nih.gov/38754271/

3. Cooke, Paul S, Nanjappa, Manjunatha K, Ko, CheMyong, Prins, Gail S, Hess, Rex A. . Estrogens in Male Physiology. In Physiological reviews, 97, 995-1043. doi:10.1152/physrev.00018.2016. https://pubmed.ncbi.nlm.nih.gov/28539434/

4. Gregorio, Karen Cristina Rego, Laurindo, Caroline Pancera, Machado, Ubiratan Fabres. 2021. Estrogen and Glycemic Homeostasis: The Fundamental Role of Nuclear Estrogen Receptors ESR1/ESR2 in Glucose Transporter GLUT4 Regulation. In Cells, 10, . doi:10.3390/cells10010099. https://pubmed.ncbi.nlm.nih.gov/33430527/

5. Ahmed, Fozia, Hetty, Susanne, Vranic, Milica, Pereira, Maria João, Eriksson, Jan W. . ESR2 expression in subcutaneous adipose tissue is related to body fat distribution in women, and knockdown impairs preadipocyte differentiation. In Adipocyte, 11, 434-447. doi:10.1080/21623945.2022.2102116. https://pubmed.ncbi.nlm.nih.gov/35856485/

6. Gallegos-Arreola, Martha Patricia, Zúñiga-González, Guillermo M, Figuera, Luis E, Gómez-Meda, Belinda Claudia, Rosales-Reynoso, Mónica Alejandra. 2022. ESR2 gene variants (rs1256049, rs4986938, and rs1256030) and their association with breast cancer risk. In PeerJ, 10, e13379. doi:10.7717/peerj.13379. https://pubmed.ncbi.nlm.nih.gov/35573183/