Regulation of Bone Cell Function by Estrogens
The biological actions of estrogens are manifest in cells expressing either of two genetically and functionally distinct estrogen receptors (ERs). Although generally considered reproductive hormones, estrogens are also key regulators of processes involved in bone homeostasis and in the cardiovascular and central nervous systems. Drugs that regulate the activity of the ERs are widely used as contraceptives, components of hormone therapy regimens in menopausal women, and breast cancer treatments/chemopreventives. Importantly, the mechanisms by which estrogens work in different tissues are not the same, and these differences can be exploited in the development of selective estrogen receptor modulators (SERMs), compounds whose relative agonist/antagonist activity can differ in different tissues. More recently developed are the tissue selective estrogen complexes (TSECs), comprised of a SERM and an estrogen. These drugs effectively treat hot flashes, exhibit useful estrogenic activity in the bone, and are inactive in the uterus and breast. Therefore, these drugs are likely to be advantageous over current hormone therapy regimens in which a progestin is required. In this chapter, a discussion of our current understanding of ER action is presented, as well as how this information has enabled a shift from empirical- to mechanism-based discovery of ER modulators. © 2013 Elsevier Inc. All rights reserved.
