Estrogen dependent signaling in reproductive tissues – A role for estrogen receptors and estrogen related receptors

► Estrogens regulate the reproductive and cardiovascular systems, the skeleton and the brain. ► Estrogen receptor (ERα, β) genes are subject to alternative splicing. ► Ratios of ER subtypes/variants in cells determines the impact of estrogens on tissue function. ► ERα, β, and ERβ variants, have unique patterns of expression in reproductive tissues. ► Estrogen related receptors (α, β, γ) may play a role in regulation of cell metabolism. Estrogens play a fundamental role in the development and normal physiological function of multiple tissue systems and have been implicated in the ontogeny of cancers. The biological effects of estrogens are classically mediated via interaction with cognate nuclear receptors. The relative expression of ER subtypes/variants varies between cells within different tissues and this alters the response to natural and synthetic ligands. This review focuses on the role of estrogen and estrogen related receptors in reproductive tissues.