Regulation of estrogen receptor beta activity and implications in health and disease

Abstract

Together with the estrogen receptor (ER) alpha, estrogen receptor beta (ER beta ) mediates many of the physiological effects of estrogens. As ER beta is crucially involved in a variety of important physiological processes, its activity should be tightly regulated. ER beta regulation is achieved by hormone binding as well as by posttranslational modifications of the receptor. Furthermore, ER beta expression levels are under circadian control and can be regulated by DNA methylation of the ER beta promoter region. There are also a number of factors that can interfere with ER beta activity, such as phytoestrogens, endocrine disruptive chemicals, and growth factors. In this article, we outline different mechanisms of ER beta regulation and how they are implicated in various diseases. We also discuss how these insights might help to specifically target ER beta in drug design.

Estrogen receptor-positive breast cancer molecular signatures and therapeutic potentials (Review)

“…Estrogen is a steroid hormone that is crucial for growth, development and reproduction (48). Estrogens have been shown to play an important role in human breast cancer development and ~1/3 of breast cancers are stimulated by estradiol (49).…”

Receptor-based virtual screening evaluation for the identification of estrogen receptorβligands

“…The ligands were then minimized using the conjugated gradient method until a convergence value of 0.05 kcal/(Å mol), using the same force field and parameters as for the conformational search. The a carbons of the ERb structures were aligned with each other using a reference structure, then each minimized ligand was docked in turn into all the 18 available X-ray structures by means of AUTODOCK 4 27 software packages. The docking results were evaluated through a comparison between the found docked positions of the ligand and the experimental ones.…”

“…On the other hand, ERb seems to have stronger effects on non-reproductive organ systems such as prostate and colon, as well as on the cardiovascular and central nervous systems. Indeed, ERb proved to be involved in several pathological states affecting these tissues 3,4 . The expression of ERb in prostate cancer and colon cancer, and its role in the development and progression of these malignancies have been extensively reviewed and discussed elsewhere 2,5 .…”

Modulation of estrogenic action in clear cell carcinoma of the ovary (Review)

“…There are a number of factors that interfere with ER expression and estrogen activity. Many factors are implicated as an important regulator of distinct aspects of ER action and expression, including gene expression, DNA methylation of the promoter region, histone deacetylation and heme and iron binding (16) (Fig. 1).…”