Segregation of nuclear and membrane-initiated actions of estrogen receptor using genetically modified animals and pharmacological tools

Estrogen receptor alpha (ER alpha) and beta (ER8) are members of the nuclear receptor superfamily, playing widespread functions in reproductive and non-reproductive tissues. Beside the canonical function of ERs as nuclear receptors, in this review, we summarize our current understanding of extra-nuclear, membrane-initiated functions of ERs with a specific focus on ER alpha. Over the last decade, in vivo evidence has accumulated to demonstrate the physiological relevance of this ER alpha membrane-initiated-signaling from mouse models to selective pharmacological tools. Finally, we discuss the perspectives and future challenges opened by the integration of extranuclear ER alpha signaling in physiology and pathology of estrogens.

Automated summary

In this review, the article summarizes the dual roles of estrogen receptors in nuclear and extra-nuclear, membrane-initiated functions, and discusses the physiological and pathological relevance and challenges posed by these functions in physiology and pathology of estrogens.