5alpha-dihydrotestosterone inhibits 1alpha,25-dihydroxyvitamin D3-induced expression of CYP24 in human prostate cancer cells

A cross-talk between 1alpha,25-dihydroxyvitamin D(3) [1alpha,25-(OH)(2)D(3)] and 5alpha-dihydrotestosterone (DHT) in the growth inhibition has been demonstrated, but the mechanism is unknown. The expression of 25-hydroxyvitamin D(3) 24-hydroxylase (24-hydroxylase) was measured using a real-time quan...

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Bibliographic Details
Published in:The Prostate 2005-05, Vol.63 (3), p.222
Main Authors: Lou, Yan-Ru, Nazarova, Nadja, Talonpoika, Riikka, Tuohimaa, Pentti
Format: Article
Language:English
Subjects:
Androgen Receptor Antagonists
Androgens - pharmacology
Anilides - pharmacology
Calcitriol - antagonists & inhibitors
Calcitriol - metabolism
Calcitriol - pharmacology
Cycloheximide - pharmacology
Cytochrome P-450 Enzyme System - genetics
Dihydrotestosterone - pharmacology
Drug Interactions
Flutamide - analogs & derivatives
Flutamide - pharmacology
Gene Expression Regulation, Enzymologic - drug effects
Humans
Male
Nitriles
Prostatic Neoplasms - enzymology
Protein Synthesis Inhibitors - pharmacology
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - analysis
Signal Transduction
Steroid Hydroxylases - genetics
Tosyl Compounds
Tumor Cells, Cultured
Vitamin D3 24-Hydroxylase
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Summary:A cross-talk between 1alpha,25-dihydroxyvitamin D(3) [1alpha,25-(OH)(2)D(3)] and 5alpha-dihydrotestosterone (DHT) in the growth inhibition has been demonstrated, but the mechanism is unknown. The expression of 25-hydroxyvitamin D(3) 24-hydroxylase (24-hydroxylase) was measured using a real-time quantitative RT-PCR assay and the catabolism of 1alpha,25-(OH)(2)D(3) was measured using a radioreceptor assay. Real-time RT-PCR showed that DHT at 1-100 nM significantly inhibited 1alpha,25-(OH)(2)D(3)-induced expression of 24-hydroxylase in LNCaP cells. Furthermore, the catabolism of 1alpha,25-(OH)(2)D(3) was decreased by 10 nM DHT. An androgen receptor (AR) antagonist, Casodex antagonized the DHT effect, whereas an AR agonist (due to the mutant AR in LNCaP cells) hydroxyflutamide did not. We demonstrated, for the first time, that DHT reduces the ability of 1alpha,25-(OH)(2)D(3) to induce 24-hydroxylase expression. Our results not only support the earlier finding of a cross-talk between androgen and vitamin D in human prostate cancer cells but also provide a possible mechanism how androgen and vitamin D signaling pathways may interact.
ISSN:0270-4137