Selective Estrogen Receptor Modulators (SERMs) and Selective Androgen Receptor Modulators (SARMs)

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Abstract

Sex hormones, androgens and estrogens, are critical not only for the physiology and development of secondary sexual organs, but also for neuronal development, cognition, bone and muscle development and maintenance, adipose tissue physiology, lipid and carbohydrate homeostasis. The phenotypes of transgenic animals in which the synthesis of androgens and estrogens or their ubiquitously expressed receptors (androgen receptor (AR, NR3C4) and estrogen receptor (ER, NRC3A1/2) has been abolished provide unequivocal evidence of their essential roles. Likewise, imbalances due to hypo- or hyperactivity of the AR and ER are associated with a variety of human diseases, including osteoporosis, sarcopenia and breast, ovarian and prostate cancers, to name a few, making steroidogenic enzymes and steroid receptors attractive therapeutic targets. Despite their endogenous roles, testosterone and estradiol are often not the first choice of treatment due to their steroidal pharmacophore and lack of tissue selectivity. Advances in the understanding of AR and ER biology and synthetic chemistry efforts to identify small molecule modulators of ER and AR that elicit favorable effects on target tissues without effects on off-target tissues led to the advent of selective estrogen receptor modulators (SERMs) and selective androgen receptor modulators (SARMs). This chapter discusses the pharmaceutical development, pharmacological characteristics, therapeutic functions, and molecular mechanisms for tissue selectivity of SERMs and SARMs.

Keywords

Androgen receptor Estrogen receptor Α/β Ligand binding domain Agonists Antagonists 
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Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.Department of MedicineDirector, Center for Cancer Drug Discover, University of Tennessee Health Science CenterMemphisUSA
  2. 2.Dean and Professor of Pharmaceutical SciencesCollege of Pharmacy, University of MichiganAnn ArborUSA

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