Age-dependent Effects of 17β-estradiol on the Dynamics of Estrogen Receptor β (ERβ) Protein–Protein Interactions in the Ventral Hippocampus

• Published in: Molecular & cellular proteomics Vol. 13; no. 3; pp. 760 - 779
• Main Authors: Mott, Natasha N., Pinceti, Elena, Rao, Yathindar S., Przybycien-Szymanska, Magdalena M., Prins, Sarah A., Shults, Cody L., Yang, Xinli, Glucksman, Marc J., Roberts, James L., Pak, Toni R.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2014; The American Society for Biochemistry and Molecular Biology
• Subjects: Adenosine Triphosphatases - metabolism; Aging - drug effects; Aging - metabolism; Animals; Annexin A5 - metabolism; Cell Cycle Proteins - metabolism; Estradiol - pharmacology; Estrogen Receptor beta - genetics; Estrogen Receptor beta - metabolism; Female; Gelsolin - metabolism; Gene Knockdown Techniques; Glyceraldehyde-3-Phosphate Dehydrogenases - metabolism; HEK293 Cells; Hippocampus - drug effects; Hippocampus - metabolism; Humans; Image Processing, Computer-Assisted; Promoter Regions, Genetic - genetics; Protein Binding - drug effects; Protein Interaction Mapping; Rats; Rats, Inbred F344; Response Elements - genetics; RNA, Small Interfering - metabolism; Subcellular Fractions - drug effects; Subcellular Fractions - metabolism; Transcription, Genetic - drug effects; Valosin Containing Protein
• ISSN: 1535-9476; 1535-9484
• DOI: 10.1074/mcp.M113.031559

Recent clinical evidence suggests that the neuroprotective and beneficial effects of hormone therapy may be limited by factors related to age and reproductive status. The patient's age and length of time without circulating ovarian hormones are likely to be key factors in the specific neurological outcomes of hormone therapy. However, the mechanisms underlying age-related changes in hormone efficacy have not been determined. We hypothesized that there are intrinsic changes in estrogen receptor β (ERβ) function that determine its ability to mediate the actions of 17β-estradiol (E2) in brain regions such as the ventral hippocampus. In this study, we identified and quantified a subset of ERβ protein interactions in the ventral hippocampus that were significantly altered by E2 replacement in young and aged animals, using two-dimensional differential gel electrophoresis coupled with liquid chromatography–electrospray ionization–tandem mass spectrometry. This study demonstrates quantitative changes in ERβ protein–protein interactions with E2 replacement that are dependent upon age in the ventral hippocampus and how these changes could alter processes such as transcriptional regulation. Thus, our data provide evidence that changes in ERβ protein interactions are a potential mechanism for age-related changes in E2 responsiveness in the brain after menopause.