A Phosphotyrosine Switch in Estrogen Receptor β Is Required for Mouse Ovarian Function

Frontiers in Cell and Developmental Biology

Yanfen Hu¹  Rong Li²  Jing Yang²  Bin Yuan²  Louis Dubeau³ 

[1] Department of Anatomy and Cell Biology, School of Medicine and Health Sciences, The George Washington University, Washington, DC, United States;Department of Biochemistry and Molecular Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, DC, United States;Department of Pathology, USC/Norris Comprehensive Cancer Center, Keck School of Medicine of University of Southern California, Los Angeles, CA, United States;

关键词: estrogen receptor beta;    knock-in;    ovary;    follicle;    fertility;   

DOI  :  10.3389/fcell.2021.649087

来源: DOAJ

【 摘 要 】

The two homologous estrogen receptors ERα and ERβ exert distinct effects on their cognate tissues. Previous work from our laboratory identified an ERβ-specific phosphotyrosine residue that regulates ERβ transcriptional activity and antitumor function in breast cancer cells. To determine the physiological role of the ERβ phosphotyrosine residue in normal tissue development and function, we investigated a mutant mouse model (Y55F) whereby this particular tyrosine residue in endogenous mouse ERβ is mutated to phenylalanine. While grossly indistinguishable from their wild-type littermates, mutant female mice displayed reduced fertility, decreased ovarian follicular cell proliferation, and lower progesterone levels. Moreover, mutant ERβ from female mice during superovulation is defective in activating promoters of its target genes in ovarian tissues. Thus, our findings provide compelling genetic and molecular evidence for a role of isotype-specific ERβ phosphorylation in mouse ovarian development and function.

【 授权许可】

Unknown