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


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 1alpha,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 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.


CONCLUSIONS
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.
Lou
Yan-Ru
YR
Department of Anatomy, Medical School, University of Tampere, Finland. loyalo@uta.fi
Nazarova
Nadja
N
Talonpoika
Riikka
R
Tuohimaa
Pentti
P
D059002:Androgen Receptor Antagonists; D000728:Androgens / Q000494:pharmacology; D000813:Anilides / Q000494:pharmacology; D002117:Calcitriol / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology*; D003513:Cycloheximide / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D013196:Dihydrotestosterone / Q000494:pharmacology*; D004347:Drug Interactions; D005485:Flutamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D008297:Male; D009570:Nitriles; D011471:Prostatic Neoplasms / Q000201:enzymology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013250:Steroid Hydroxylases / Q000235:genetics*; D014105:Tosyl Compounds; D014407:Tumor Cells, Cultured; D065668:Vitamin D3 24-Hydroxylase
D059002:Androgen Receptor Antagonists; D000728:Androgens; D000813:Anilides; D009570:Nitriles; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D014105:Tosyl Compounds; D013196:Dihydrotestosterone; C014290:hydroxyflutamide; D005485:Flutamide; D003577:Cytochrome P-450 Enzyme System; D003513:Cycloheximide; C053541:bicalutamide; D013250:Steroid Hydroxylases; D065668:Vitamin D3 24-Hydroxylase; D002117:Calcitriol