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

BACKGROUND. A cross-talk between la,25-dihydroxyvitamin D-3 [1 alpha.,25-(OH)(2)D-3] and 5 alpha-dihydrotestosterone (DHT) in the growth inhibition has been demonstrated, but the mechanism is unknown. METHODS. 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 1 alpha,25-(OH)(2)D-3 was measured using a radioreceptor assay. RESULTS. Real-time RT-PCR showed that DHT at 1-100 nM significantly inhibited 1 alpha,25-(OH)(2)D-3-induced expression of 24-hydroxylase in LNCaP cells. Furthermore, the catabolism of 1 alpha,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. CONCLUSIONS. We demonstrated, for the first time, that DHT reduces the ability of 1 alpha,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. (c) 2004 Wiley-Liss. Inc.