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

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Nuclear Receptors: From Structure to the Clinic

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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.

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Authors and Affiliations

  1. Department of Medicine, Director, Center for Cancer Drug Discover, University of Tennessee Health Science Center, Memphis, USA

    Ramesh Narayanan (Associate Professor)

  2. Dean and Professor of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, Michigan, USA

    James T. Dalton

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  1. Ramesh Narayanan
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  2. James T. Dalton
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Correspondence to James T. Dalton .

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Editors and Affiliations

  1. School of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom

    Iain J. McEwan

  2. Department of Basic Sciences, The Commonwealth Medical College, Scranton, Pennsylvania, USA

    Raj Kumar

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Narayanan, R., Dalton, J. (2015). Selective Estrogen Receptor Modulators (SERMs) and Selective Androgen Receptor Modulators (SARMs). In: McEwan, I., Kumar, R. (eds) Nuclear Receptors: From Structure to the Clinic. Springer, Cham. https://doi.org/10.1007/978-3-319-18729-7_11

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