The selective oestrogen receptor modulators idoxifene and raloxifene have fundamentally different cell-specific oestrogen-response element (ERE)-dependent/independent mechanisms in vitro

Idoxifene and raloxifene are selective oestrogen receptor modulators (SERMs ) that by definition exhibit tissue-specific agonist or antagonist properti es via interactions with the oestrogen receptor (ER). Idoxifene acts as an oestrogen agonist in osteoblastic cells via an ER/ERE-mediated mechanism. I n contrast, raloxifene is an antagonist via the ERE in osteoblastic cells. Like the pure antagonist ICI 182,780, raloxifene inhibited the potent agoni st activity of both 17 beta -oestradiol and idoxifene through the ERE where as idoxifene had no effect on the agonist activity of 17 beta -oestradiol v ia the ERE. In breast cancer cells, both raloxifene and idoxifene were pote nt antagonists of ERE-mediated 17 beta -oestradiol action suggesting an ERE -dependent mechanism of action for both ligands in these cells. Therefore, these SERMs exhibit cell-specific ERE-dependent and -independent mechanisms of action. (C) 2000 Elsevier Science Ltd. All rights reserved.