Retinol Research Today is a free monthly online journal that collates and summarizes the latest research about Retinol, including details on vitamin a, uses, wrinkle treatment, anti-aging.

Retinoic acid via RARalpha inhibits the expression of 24-hydroxylase in human prostate stromal cells.

Lou YR, Miettinen S, Kagechika H, Gronemeyer H, Tuohimaa P

Department of Anatomy Medical School, FIN-33014 University of Tampere, Finland. loyalo@uta.fi

25-Hydroxyvitamin D(3)-24-hydroxylase (24-hydroxylase) is an important inactivating enzyme and its expression is induced by 25-hydroxyvitamin D3 (25OHD3) and 1alpha,25-dihydroxyvitamin D3 (1alpha,25-(OH)2D3) through action of heterodimers of vitamin D receptor (VDR) and retinoid X receptor (RXR). RXRs also act as heterodimer partners for retinoic acid receptors (RARs), mediating the action of all-trans-retinoic acid (ATRA). Prostate stroma plays a crucial role in prostate cancer development and benign prostatic hyperplasia. We demonstrate here that ATRA markedly reduced the expression of 24-hydroxylase mRNA induced by 25OHD3 and 1alpha,25-(OH)2D3 in human prostatic stromal cells P29SN and P32S but not in epithelial cells PrEC or cancer cells LNCaP. By using transfection and RAR-selective ligands, we found that the inhibitory effect of ATRA on 24-hydroxylase expression in stromal cells was mediated by RARalpha but not by RARbeta. Moreover, the ATRA-induced expression of RARbeta was also mediated by RARalpha. The combined treatment of 1alpha,25-(OH)2D3 and RARalpha agonist Am80 at 10 nM exhibited strong growth-inhibitory effect whereas either alone had no effect. Our data suggest that ATRA suppresses 24-hydroxylase expression through RARalpha-dependent signaling pathway and can enhance vitamin D action in suppression of cell growth.

Published 23 November 2005 in Biochem Biophys Res Commun, 338(4): 1973-81.
Full-text of this article is available online (may require subscription).

© 2004-2008 Retinol Research Today. All Rights Reserved.