DEVELOPMENT OF SPECIFIC BIOLUMINESCENT IN-VITRO ASSAYS FOR SELECTING POTENTIAL ANTIMINERALOCORTICOIDS

Efficient antimineralocorticoid selection requires a reliable, discrim inating and easy assay for monitoring biological activity of not only the specific receptor, but also closely related receptors such as gluc ocorticoid and progestin. These related activities should be as low as possible to obtain specific antimineralocorticoid compounds. In this paper, we describe two cellular models used for easy and specific meas urement of mineralocorticoid and progestin activities. These models in volve the induction of firefly luciferase under hormonal control media ted by a chimeric receptor. The first model comprises transiently tran sfected MCF-7 cells, whereas the second uses stably transfected HeLa c ells. Glucocorticoid activity was assayed with the classic tyrosine-am inotransferase induction method in HTC cells. Six compounds of a new f amily of 11 beta-substituted-17-spirolactone steroids were thus studie d and compared to control compounds. Five of them showed antimineraloc orticoid activity and one was active at a concentration lower than tha t of mespirenone.