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5α‐dihydrotestosterone inhibits 1α,25‐dihydroxyvitamin D 3 ‐induced expression of CYP24 in human prostate cancer cells
Author(s) -
Lou YanRu,
Nazarova Nadja,
Talonpoika Riikka,
Tuohimaa Pentti
Publication year - 2005
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20189
Subject(s) - dihydrotestosterone , prostate cancer , prostate , cancer , medicine , cancer research , endocrinology , oncology , androgen , hormone
BACKGROUND A cross‐talk between 1α,25‐dihydroxyvitamin D 3 [1α,25‐(OH) 2 D 3 ] and 5α‐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 1α,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 1α,25‐(OH) 2 D 3 ‐induced expression of 24‐hydroxylase in LNCaP cells. Furthermore, the catabolism of 1α,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 1α,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. © 2004 Wiley‐Liss, Inc.