The dynamics of estrogen receptor activity

In the latest few years, the merging of imaging and animal engineering technologies has led to the generation of innovative tools that provide the opportunity to look into the dynamics of specific molecular events in living animals during their entire life under a completely renewed perspective. These tools will have a profound impact not only on basic research, but also on drug discovery and development allowing to depict the activity of any therapeutic agents in all their designed targets as well as in the organs where they may cause undesired effects. Along this research line, our laboratory has recently described the first animal model reporting the state of activity of estrogen receptors (ERs) in real time: the ERE-luc reporter mouse. The application of optical imaging to the ERE-luc has allowed an unprecedented in depth view of estrogen signaling in all of its target tissues. For example, the analysis of the state of activity of ERs in the physiological setting of the estrous cycle has provided compelling evidence that hormone-independent mechanisms are responsible for activating ERs in non-reproductive organs. This discovery may pave the way to a rational basis for the development of novel, more selective and effective treatments for menopause.