Estrogen receptors in health and disease

Estrogen signalling is a balance between two closely related transcription factors (TFs), the estrogen receptors (ERα and ERβ), both of which bind to similar DNA element called estrogen response element (ERE). ERs do not function by themselves but require a number of co-regulatory proteins (SRC1, A1, NCoR) whose cell-speciûc expression elucidates some of the divergent cellular actions of estrogen. A considerable body of evidence has shown that over-expression of ERα leads to uncontrolled cell growth and proliferation resulting in carcinomas of breast, ovary, uterus and prostate while ERβ down-regulation causes colon cancer. ERs are well-known regulators of several aspects of metabolism, including glucose and lipid metabolism, whereas impaired estrogen signalling is associated with the development of metabolic bone disorders as in post-menopausal women. We review new evidences depicting the importance of ER in understanding the normal physiological functions and how the disruption of typical estrogen signalling leads to the development and progression of various forms of endocrine cancers and metabolic disorders including post-menopausal osteoporosis, diabetes and obesity. Re-examination of available therapies will enable us to therapeutically address fundamental issues towards the design of pharmacologic molecules so as to target crucial metabolic cascades and genes.