Intracrine androgen metabolism in prostate cancer progression: mechanisms of castration resistance and therapeutic implications

Best Pract Res Clin Endocrinol Metab. 2008 Apr;22(2):243-58. doi: 10.1016/j.beem.2008.01.003.


Residual tissue androgens are consistently detected within the prostate tumors of castrate individuals and are thought to play a critical role in facilitating the androgen receptor-mediated signaling pathways leading to disease progression. The source of residual tumor androgens is attributed in part to the uptake and conversion of circulating adrenal androgens. Whether the de novo biosynthesis of androgens from cholesterol or earlier precursors occurs within prostatic tumors is not known, but it has significant implications for treatment strategies targeting sources of androgens exogenous to the prostate versus 'intracrine' sources within the prostatic tumor. Moreover, increased expression of androgen-metabolizing genes within castration-resistant metastases suggests that up-regulated activity of endogenous steroidogenic pathways may contribute to the outgrowth of 'castration-adapted' tumors. These observations suggest that a multi-targeted treatment approach designed to simultaneously ablate testicular, adrenal and intracrine contributions to the tumor androgen signaling axis will be required to achieve optimal therapeutic efficacy.

Publication types

  • Evaluation Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Androgens / analysis
  • Androgens / metabolism*
  • Animals
  • Antineoplastic Agents, Hormonal / therapeutic use*
  • Biosynthetic Pathways / drug effects
  • Biosynthetic Pathways / physiology
  • Disease Progression
  • Drug Resistance, Neoplasm / physiology*
  • Enzyme Inhibitors / therapeutic use
  • Humans
  • Male
  • Models, Biological
  • Orchiectomy / methods
  • Paracrine Communication / physiology
  • Prostate / chemistry
  • Prostate / metabolism
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology*


  • Androgens
  • Antineoplastic Agents, Hormonal
  • Enzyme Inhibitors