Steroid biosynthesis and prostate cancer

Nima Sharifi, Richard J. Auchus

Research output: Contribution to journalReview article

59 Scopus citations

Abstract

The pathways of androgen biosynthesis in human beings have been studied for decades, and the major pathways and enzymes responsible for testosterone and dihydrotestosterone synthesis are now well described. Minor or alternate pathways, which might contribute substantially to androgen production in specific states, have also emerged. Likewise, the requirement of androgen for prostate formation and growth date back over a half-century, and the dependence of prostate cancer on androgens has been known and exploited for as long. Despite the success of testicular removal or suppression, androgen receptor antagonists, and androgen synthesis inhibitors in the treatment of prostate cancer, the sources of androgen, their routes of synthesis, and the contributions of various routes remain topics of debate, particularly in castration-resistant disease when circulating androgens are very low. Here we review the major pathways of 19-carbon steroid synthesis in the adrenal and gonad, peripheral pathways to active androgens, and recent data charting flux of androgen precursors in prostate cancer. We are far from a unified understanding of androgen generation in prostate cancer, but the similarities and differences from glandular androgen synthesis that have already emerged provide important clues to designing the next generation of treatments for this common and devastating disease.

Original languageEnglish (US)
Pages (from-to)719-726
Number of pages8
JournalSteroids
Volume77
Issue number7
DOIs
StatePublished - Jun 2012

Keywords

  • Abiraterone acetate
  • Androgen receptor
  • Dihydrotestosterone
  • Prostate cancer
  • Steroidogenesis
  • Testosterone

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology
  • Pharmacology
  • Clinical Biochemistry
  • Organic Chemistry

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