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Importance of the intracrine metabolism of adrenal androgens in androgen-dependent prostate cancer.

Suzuki K, Nishiyama T, Hara N, Yamana K, Takahashi K, Labrie F

1Division of Urology, Department of Regenerative and Transplant Medicine, Course of Biological Function and Medicine Control, Niigata University Graduate School of Medical and Dental Science, Niigata, Japan.

The metabolic pathways of androgens and processes by which androgens induce re-growth after androgen deprivation therapy in prostate cancer have not been fully elucidated. In this study, finasteride decreased PSA secretion in medium containing testosterone, androstenedione, androstenediol and dehydroepiandrosterone, whereas dihydrotestosterone (DHT)- and hydroxy-flutamide-induced PSA production was not inhibited by finasteride in LNCaP-FGC cells. The present data show that adrenal androgen precursors do not directly interact with androgen receptors (ARs) but are converted to DHT via the intraprostatic metabolic pathways, resulting in the induction of LNCaP activity. This is the first report confirming this mechanism experimentally and also suggest the use of combined therapies that target ARs and prevent the formation of DHT within prostate cancer cells to achieve optimal therapeutic efficacy.Prostate Cancer and Prostatic Diseases advance online publication, 27 March 2007; doi:10.1038/sj.pcan.4500956.

Published 27 March 2007 in Prostate Cancer Prostatic Dis.
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