Upon binding to 17-β-estradiol, estriol or related ligands, the encoded protein forms homo-dimers or hetero-dimers with estrogen receptor α that interact with specific DNA sequences to activate transcription.
[19][20] Similarly, overexpression of ERβ via lentiviral infection in mature virgin female rats decreases mammary proliferation.
[17] Expression of ERα and ERβ in the mammary gland have been found to vary throughout the menstrual cycle and in an ovariectomized state in female rats.
Polymorphism may affect ERβ function and lead to altered responses in postmenopausal women receiving hormone replacement therapy.
[30] Mutations in ERβ have been shown to influence cardiomyocytes, the cells that comprise the largest part of the heart, and can lead to an increased risk of cardiovascular disease (CVD).
Many types of ERβ receptors exist in order to help regulate gene expression and subsequent health in the body, but binding of 17βE2 (a naturally occurring estrogen) specifically improves cardiac metabolism.
The ERβ signaling pathway plays a role in both vasodilation and arterial dilation, which contributes to an individual having a healthy heart rate and a decrease in blood pressure.
Thus, alterations in this signaling pathways due to ERβ mutation could lead to myocyte cell death from physiological stress.
Similar to CVD, post-menopausal women have an increased risk of developing Alzheimer's disease (AD) due to a loss of estrogen, which affects proper aging of the hippocampus, neural survival and regeneration, and amyloid metabolism.
ERβ helps by up-regulating insulin-degrading enzyme (IDE), which leads to β-amyloid degradation when accumulation levels begin to rise.
APOE expression in the hippocampus is specifically regulated by 17βE2, affecting learning and memory in individuals afflicted with AD.
Variations in endogenous estrogen levels cause changes in dendritic architecture in the hippocampus, which affects neural signaling and plasticity.
Specifically, lower estrogen levels lead to decreased dendritic spines and improper signaling, inhibiting plasticity of the brain.