Androgen Receptor Coactivators and Prostate Cancer

  • Irina U. Agoulnik
  • Nancy L. Weigel
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 617)

Among USA men, prostate cancer (PC) is the second most common cause of death from cancer. Thus, the etiology, prevention, and treatment of the disease are a major health concern. Development and differentiation of the prostate is androgen dependent and PC, too, is androgen dependent (1). Consequently, some form of androgen deprivation is the primary treatment for metastatic PC. Although effective initially in reducing tumor burden, the tumors become resistant to androgen deprivation and recur within a relatively short period of time. The actions of androgens are mediated by the androgen receptor (AR) a hormone-activated transcription factor, which belongs to the large nuclear receptor superfamily of ligand-activated transcription factors (2, 3). AR differs from many of the other receptors in that it has two natural endogenous ligands. Testosterone (T) (Fig. 1) is the major circulating androgen and is the major hormone in most tissues. T is produced in the testis and is converted to 5α-dihydrotestosterone (DHT) (Fig. 1) by the enzyme 5α-reductase in the prostate as well as in selected other tissues including skin. DHT is a higher affinity ligand and is functionally the most important androgen in the prostate. In addition, there are a number of androgen metabolites including DHEA and androstenediol, which have much lower affinities for AR. Although these androgens are not thought to play a major role in AR action in androgen-repleted males, they may activate the AR when levels of T and DHT are reduced as a result of androgen ablation therapy.


Prostate Cancer Androgen Receptor LNCaP Cell Steroid Receptor DU145 Cell 
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Copyright information

© Springer 2008

Authors and Affiliations

  • Irina U. Agoulnik
  • Nancy L. Weigel
    • 1
  1. 1.Dept. of Molecular and Cellular BiologyBaylor College of MedicneHoustonUSA

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