Estrogen Receptors: Therapies Targeted to Receptor Subtypes

Abstract

Over the past two decades, we have learned that estrogens play important physiological roles not only in women but also in men and that the biological effects of estrogen are mediated by not one but two distinct estrogen receptors (ERs), ERα and ERβ. Our appreciation of the physiological importance of estrogen and the mechanisms by which it acts has significantly increased over the years; however, we are only now beginning to decipher the roles of ERα and ERβ in different organs and to elucidate how selective ligands, acting through either of the two ERs, can prevent or treat various age- or sex-specific diseases. The specific roles of ERα and ERβ and the therapeutic potential of ER subtype-selective agonists in bone and metabolic homeostasis, depression, vasomotor symptoms, neurodegenerative diseases, and cancer are reviewed herein. It must be stated, however, that appropriate clinical studies are necessary to validate these compounds as agents for the prevention and treatment of diseases.

Inhibitory effect of estrogen receptor beta on P2X3 receptors during inflammation in rats

“…ERβ is widely expressed on small-sized nociceptive DRG neurons and the colon, suggesting modulation in peripheral pain signal transduction [38][39][40]. Reports have shown that the selective ERβ agonist ERB-131 regulated nociception during the inflammatory state [18,19,41].…”

In Vivo Imaging of Brain Estrogen Receptors in Rats: A 16α-18F-Fluoro-17β-Estradiol PET Study

“…Two classes of ERs have been identified: the intracellular nuclear receptors ERa and ERb and the G protein-coupled ER (2,3). Estrogens easily diffuse through the blood-brain barrier to occupy ERs localized in specific brain regions to exert important regulatory effects on neuronal functioning and behavior (1). However, estrogens not only are produced by the ovaries but also can be produced locally inside the brain.…”

“…In addition, estrogens are involved in brain processes (1). The actions of estrogens are mediated by specialized hormone receptors, called estrogen receptors (ERs).…”

Given breast cancer, is fat better than thin? Impact of the estrogen receptor beta gene polymorphisms

“…The classical estrogen receptor, i.e., estrogen receptor alpha (ERα), was discovered in the 1960s and is encoded by the ESR1 gene located on chromosome 6, whereas the more recently identified estrogen receptor beta (ERβ) is encoded by the ESR2 gene located on chromosome 14 [21]. Many studies have investigated the prognostic and predictive role of the immunohistochemical expression of ERβ and thus observed a survival benefit and an enhanced response to tamoxifen treatment in women with high ERβ expression [12,13,28].…”