Regulation of aromatase and 5alpha-reductase by 25-hydroxyvitamin D(3), 1alpha,25-dihydroxyvitamin D(3), dexamethasone and progesterone in prostate cancer cells

J Steroid Biochem Mol Biol. 2005 Feb;94(1-3):151-7. doi: 10.1016/j.jsbmb.2005.01.024. Epub 2005 Feb 17.

Abstract

Estrogens and androgens are proposed to play a role in the pathogenesis of prostate cancer. The effective metabolites, estradiol and 5alpha-dihydrotestosterone are produced from testosterone by aromatase and 5alpha-reductase, respectively. Metabolites of vitamin D have shown to inhibit the growth of prostate cancer cells. The aim of the present study was to verify whether 25-hydroxyvitamin D(3) (25OHD(3)), 1alpha,25-dihydroxyvitamin D(3) [1alpha,25-(OH)(2)D(3)], dexamethasone, and progesterone regulate the expression of aromatase and 5alpha-reductase in human prostate cancer cells. LNCaP and PC3 cells were treated with 25OHD(3), 1alpha,25-(OH)(2)D(3), dexamethasone, or progesterone. Aromatase and 5alpha-reductase mRNA was quantified by real-time RT-PCR and aromatase enzyme activity was measured by the [(3)H] water assay. Aromatase enzyme activity in LNCaP and PC3 cells was increased by both 10nM dexamethasone, 1-100 nM 1alpha,25-(OH)(2)D(3) and 100 nM-10 microM progesterone. The induction was enhanced when hormones were used synergistically. Real-time RT-PCR analysis showed no regulation of the expression of aromatase mRNA by any steroids tested in either LNCaP or PC3 cells. The expression of 5alpha-reductase type I mRNA was not regulated by 1alpha,25-(OH)(2)D(3) and no expression of 5alpha-reductase type II was detected in LNCaP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Oxo-5-alpha-Steroid 4-Dehydrogenase / drug effects
  • 3-Oxo-5-alpha-Steroid 4-Dehydrogenase / genetics*
  • 3-Oxo-5-alpha-Steroid 4-Dehydrogenase / metabolism*
  • Aromatase / drug effects
  • Aromatase / genetics*
  • Aromatase / metabolism*
  • Calcifediol / pharmacology*
  • Calcitriol / pharmacology*
  • Cell Division / drug effects
  • Cell Line, Tumor
  • Dexamethasone / pharmacology*
  • Gene Expression Regulation, Enzymologic / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Male
  • Progesterone / pharmacology*
  • Prostatic Neoplasms
  • RNA, Messenger / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription, Genetic / drug effects

Substances

  • RNA, Messenger
  • Progesterone
  • Dexamethasone
  • Aromatase
  • 3-Oxo-5-alpha-Steroid 4-Dehydrogenase
  • Calcitriol
  • Calcifediol