Health & Environmental Research Online (HERO)


Print Feedback Export to File
7350455 
Book/Book Chapter 
ANDROGEN RECEPTOR 
Dalton, JT; Gao, W 
2010 
Proteins and Cell Regulation 
8 
143-182 
WOS:000276683200006 
Androgen receptor (NR3C4, or AR) is another important steroid hormone receptor that is activated by endogenous androgens, mainly testosterone and 5 alpha-dihydrotestosterone (5 alpha-DHT). AR function can be regulated by the binding of its ligands, either agonists or antagonists, which initiate sequential conformational changes of the receptor that will affect receptor function. At the cellular level, AR mainly acts as a transcription factor to regulate downstream target genes expression, while emerging research also revealed that nongenomic actions contribute to AR signaling and function. AR mediates the physiological actions of androgen, which is responsible for male sexual differentiation and pubertal changes. Historically, various steroidal androgens were used to treat androgen-related endocrine disorders, but the advent of aromatase inhibitors and recombinant erythropoietin supplanted the use of androgens in many of these conditions. With the rapidly increasing knowledge of AR protein structure and molecular mechanism of action in the last few decades, a large variety of nonsteroidal ligands, have been developed to selectively modulate AR action with much improved tissue and/or function specificity and safety profiles as compared to steroids, which could greatly expand the therapeutic uses of androgens. This chapter will focus on the chemistry and structural biology of AR, and its role and potential as drug target in disease treatment, with emphasis on the recent development of selective androgen receptor modulators (SARMs). We will provide a brief introduction of AR structure and function, followed by a detailed discussion of well-characterized synthetic AR ligands (steroidal and nonsteroidal), with integrated discussions regarding the molecular mechanism of action and potential therapeutic applications for both existing and emerging classes of AR ligands.