Chapter 19. Estrogen Receptor Modulators: Effects in Non-Traditional Target Tissues

Abstract

Publisher Summary Till date a variety of steroidal and nonsteroidal compounds that interact with the estrogen receptor (ER) have been developed as contraceptives and for the treatment of breast cancer, uterine dysfunction, and other disorders of the female reproductive system, and they have been recently reviewed. This chapter discusses primarily the effects of these estrogen receptor (ER) modulators in nonmammary tissue. The discussion here has been divided into four segments and classified compounds on the basis of their ability to mimic the effects of estrogen in skeletal and/or cardiovascular tissue and to induce uterine stimulation. This classification is consistent with the recently proposed classification on the basis of distinct DNA transcriptional profiles observed for the different classes. By far, the most investigated of the nonsteroidal ER modulators are the triphenylethylenes (TPEs). Originally investigated as contraceptives, compounds, such as tamoxifen, have been developed for the treatment of breast cancer on the basis of strong antagonism of estrogen action in mammary tissue. Only recently, the estrogen agonist activities of these compounds in the skeletal and cardiovascular systems have been researched. Although they partially antagonize the effects of estrogen on the uterus, evidence till date suggests that in the absence of estrogen the members of this structural class also tend to induce some level of uterine stimulation, hence they are classified here as partial agonists.