Activity of three selective estrogen receptor modulators on hormone-dependent responses in the mouse uterus and mammary gland.

摘要: Selective estrogen receptor modulators (SERMs) have the unique potential to provide estrogenic effects in skeletal and cardiovascular system, while minimizing/eliminating side on reproductive organs. However, despite unifying characteristic of mixed (ER) agonist/antagonist activity, compounds within this class are not interchangeable. In order define compare SERMs different hormone-responsive tissues, we evaluated bazedoxifene acetate (BZA), lasofoxifene (LAS) raloxifene (RAL) mammary gland uterus ovariectomized mouse. Endpoints measured included those regulated by estradiol alone (uterine wet weight, uterine G protein-coupled 105 (GPR105) mRNA expression indoleamine-pyrrole 2,3 dioxygenase (INDO) expression) as well others that required combination progesterone serine protease inhibitor Kazal type 3 (Spink3) expression, morphology defensin beta1 (Defbeta1) expression). The three tested had variable agonist antagonist activity these endpoints. uterus, were agonists/antagonists estradiol-induced weight increase, whereas all antagonists GPR105 expression. presence progesterone, BZA RAL agonists Spink3 LAS was primarily an antagonist. gland, predominantly endpoint clear Defbeta1 E+P-dependent marker. Finally, INDO only activity. These results demonstrate with small structural differences can elicit distinct biological responses, general, tended behave more endpoints requiring progesterone.