In vivo dynamics of estrogen receptor activity : the ERE-Luc model

In recent years several studies demonstrated the presence of estrogen receptors in mammalian tissues and significantly improved our understanding of their ability to control biological processes in reproductive as well as non-reproductive organs. Considering the manifold mechanisms and organs that are involved in estrogen action and the implication of estrogens in human female physiology, innovative approaches are required to shed light on the widespread activities of estrogen receptors in woman physiology. This is particularly relevant for the definition of novel, more efficacious hormonal replacement therapies or for the evaluation of the risk associated with the exposure to endocrine disruptors. The introduction of genetic engineering and the development and application of in vivo imaging techniques offer new tools for pre-clinical studies. The generation of the ERE-Luc mouse, a reporter animal developed for in vivo studies of the estrogen receptor activity, allows assessing the activity state of the ER signaling pathway in all target tissues and organs at once, under physiological stimuli or as a result of a pharmacological treatment. This review summarizes the main steps in the generation and appraisal of the estrogen receptor reporter mouse ERE-Luc, designed for in vivo molecular imaging studies, and describes examples demonstrating the suitability of the ERE-Luc model for drug development and for the investigation of the effects of endogenous, environmental, and dietary estrogens in vivo.