Health & Environmental Research Online (HERO)


Print Feedback Export to File
7354117 
Journal Article 
Regulation of CYP3A4 and CYP3A5 expression and modulation of "intracrine" metabolism of androgens in prostate cells by liganded vitamin D receptor 
Maguire, O; Pollock, C; Martin, P; Owen, A; Smyth, T; Doherty, D; Campbell, MJ; Mcclean, S; Thompson, P 
2012 
1 
Molecular and Cellular Endocrinology
ISSN: 0303-7207
EISSN: 1872-8057 
364 
1-2 
54-64 
English 
22939842 
WOS:000311017200005 
We investigated the capacity for vitamin D receptor (VDR) to modulate the expression of CYP3A4 and other genes that may facilitate the oxidative inactivation of androgens such as testosterone and androstanediol within prostate cells. We report that exposure to the active hormonal form of vitamin D markedly increased gene expression of CYP3A4 and CYP3A5 and ultimately achieved levels of intracellular CYP3A enzyme activity within LNCaP prostate cancer cells that were comparable to that observed for Caco2 cells, an established model of CYP3A induction, and resulted in the increased turnover of testosterone to its inactive 6β-OH metabolite. We demonstrate that VDR directs CYP3A4 and CYP3A5 expression through binding to distinct regulatory motifs located within the 5' promoter regions of both genes. The current data highlight the potential application of VDR-based treatment regimes as a means to limit the bioavailability of growth-promoting androgens within the tumor microenvironment.