The use of ERE-Luc reporter mice to monitor estrogen receptor transcriptional activity in a spatio-temporal dimension

In spite of the fact that women spend 1/3 of their lives in post-menopause, the search for appropriate therapies able to counteract the derangements associated with the menopause still represents a sort of sought after the “Holy Grail”. Nowadays, the combination of estrogens and selective estrogen receptor modulators (SERMs) - a class of compounds with a mixed agonist/antagonistic activity on the estrogen receptor (ER) in various tissues – represents the most promising approach to improve post-menopausal women’s health, by preserving the benefits while avoiding the side-effects of estrogen-based therapy. Given their complex mechanism of action, the evaluation of SERMs activity in combination with conjugated estrogens (CE) requires a multifactorial analysis that takes into account the multifaceted and dynamic effects of these compounds in target tissues, even in relation to the physiological/pathological status. To accomplish such a goal, we took advantage of the ERE-Luc model, a reporter mouse that allows the monitoring of ER transcriptional activity in a spatio-temporal dimension. Cluster analyses performed on in vivo/ex vivo bioluminescence (BLI) data and ex vivo luciferase activity enabled to sustain the combination of CE plus bazedoxifene (TSEC, tissue selective estrogen complex) as a valuable option for the pharmacological treatment of the post-menopause.