Estrogen receptors and human disease

Abstract

Estrogens influence many physiological processes in mammals, including but not limited to reproduction, cardiovascular health, bone integrity, cognition, and behavior. Given this widespread role for estrogen in human physiology, it is not surprising that estrogen is also implicated in the development or progression of numerous diseases, which include but are not limited to various types of cancer (breast, ovarian, colorectal, prostate, endometrial), osteoporosis, neurodegenerative diseases, cardiovascular disease, insulin resistance, lupus erythematosus, endometriosis, and obesity. In many of these diseases, estrogen mediates its effects through the estrogen receptor (ER), which serves as the basis for many therapeutic interventions. This Review will describe diseases in which estrogen, through the ER, plays a role in the development or severity of disease.

Icariin from Epimedium brevicornum Maxim promotes the biosynthesis of estrogen by aromatase (CYP19)

“…Icariin was identified to be the bioactive compound in Epimedium brevicornum to promote estrogen biosynthesis in KGN cells, an effect that operated in a concentration-and time-dependent manner, but more work is needed to isolate other estrogen biosynthesis-promoting compounds from the extracts of this medicinal plant. Epidemiological studies have suggested the involvement of estrogen insufficiency in cardiovascular, neurodegenerative, and inflammatory diseases (Deroo and Korach, 2006). Epimedium brevicornum and icariin have been reported to protect against heart failure, reduce the inflammatory response, and improve learning and memory, but the mechanisms for these effects are still unknown (Ma et al, 2011;Wu et al, 2012).…”

Autoantibodies to estrogen receptor α interfere with T lymphocyte homeostasis and are associated with disease activity in systemic lupus erythematosus

“…The involvement of estrogens, which influence many physiologic processes, has been shown in the development or progression of several autoimmune disorders (1)(2)(3)(4). There is evidence that 17␤-estradiol directly modulates the development and function of immune cells, although the mechanism by which this might occur is not well understood (5,6).…”

Interaction between p53 and estradiol pathways in transcriptional responses to chemotherapeutics

“…Therapeutic protocols often include modulation of either or both transcription factors, using p53-inducing drugs, such as DOX or 5FU, as well as ER antagonists or inhibitors of estrogen synthesis (www.chemocare.com). 9,38 Other examples of crosstalk between different drugs in breast and other cancer types have been recently reported. [39][40][41] Those findings exemplify the relevance of examining the impact of combinatorial treatments at the genome level.…”

“…While ERs are master regulators essential for development and maintenance of normal sexual and reproductive functions, they can also play a role in the cardiovascular, musculoskeletal, immune and central nervous systems. [8][9][10] These two diverse networks exhibit crosstalk that can be due to direct interaction between p53 and the ERs, with the more frequently described outcome being repression of p53 activity, [11][12][13][14] although p53 can also inhibit ERα. 15,16 The inhibitory crosstalk, which can be mediated by physical interactions between the two proteins, can be relieved by stress-dependent post-translational modifications of p53.…”