Abstract
Our view of estrogen signalling has undergone a paradigm shift over the recent 10–15 years with the discovery of a second estrogen receptor, ERβ, in 1995 and the finding that estrogens play an important role also in male physiology. Aromatase deficient patients and aromatase knock-out mice have highlighted the importance of estrogens in development and metabolic homeostasis while ER knock-out mice, ERα–/– and ERβ–/–, have shown that both ERs are of physiological importance and that ERα and ERβ have distinct and non-overlapping functions in the body. The uses of ER subtype-selective ligands in various animal models have further substantiated the distinctive physiological roles of ERα and ERβ and shown that they, in many contexts, are antagonistic against one another. Structural studies of the ligand-binding domains of ERα and ERβ have provided in-depth information on ligand recognition, receptor activation, and recruitment of coregulators. The cloning of coregulators and chromatin modulators together with sophisticated methodology to study gene regulation has significantly increased our understanding of cellular and target gene responses to estrogens, SERMs, and ER subtype-selective ligands.
This book chapter will review our current understanding of the mechanisms of ERα- and ERβ-dependent estrogen signalling, the role of ERα and ERβ in health and disease, and the potential clinical uses of ERα- and ERβ-selective pharmaceuticals.
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Nilsson, S., Gustafsson, JÅ. (2010). Estrogen Receptors: Their Actions and Functional Roles in Health and Disease. In: Bunce, C., Campbell, M. (eds) Nuclear Receptors. Proteins and Cell Regulation, vol 8. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-3303-1_5
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