TY  - JOUR
A1  - Fritzsche, Britta
A1  - Schuchardt, Jan-Philipp
A1  - Schmidt, Anja
A1  - Nau, Heinz
A1  - Schweigert, Florian J.
A1  - Ruehl, Ralph
T1  - CYP26A1-specific antagonist influence on embryonic implantation, gene expression and endogenous retinoid concentration in rats
N2  - Retinoids are essential in vertebrate reproduction and embryonic development. All-trans-retinoic acid (ATRA) is tightly regulated during these processes. CYP26A1 is mainly responsible for its degradation. To study the role of CYP26A1 during implantation, we applied R115866, a CYP26A1-specific antagonist, to rats during early gestation days (GD). On GD 6.5 and 12 samples were collected and the number of embryos was evaluated. ATRA concentration increased in uterus and serum, mRNA expression of CYP26A1 and CRABP2 increased in the liver, but not in the uterus. Uterine COX1 and 17 beta HSD mRNA expression was decreased. The number of embryos on GD 12 was not altered in this setting. It can be concluded that uterine expression of the analyzed retinoid-response genes during early gestation is not altered by this R115866 treatment and instead indirectly via ATRA. From our experiment we cannot confirm that ATRA obtains a major influencing role in the regulation of embryonic implantation.
Y1  - 2010
UR  - http://www.sciencedirect.com/science/journal/08906238
U6  - https://doi.org/10.1016/j.reprotox.2010.05.005
SN  - 0890-6238
ER  - 
TY  - JOUR
A1  - Szanto, Attila
A1  - Benko, Szilvia
A1  - Szatmari, István
A1  - Balint, Balint L.
A1  - Furtos, Ibolya
A1  - Ruehl, Ralph
A1  - Molnar, Sandor
A1  - Csiba, Laszlo
A1  - Garuti, Rita
A1  - Calandra, Sebastiano
A1  - Larsson, Hanna
A1  - Diczfalusy, Ulf
A1  - Nagy, Laszlo
T1  - Transcriptional regulation of human CYP27 integrates retinoid, peroxisome proliferator-activated receptor, and liver X receptor signaling in macrophages
N2  - Cholesterol uptake and efflux are key metabolic processes associated with macrophage physiology and atherosclerosis. Peroxisome proliferator-activated receptor gamma (PPARgamma) and liver X receptor alpha (LXRalpha) have been linked to the regulation of these processes. It remains to be identified how activation of these receptors is connected and regulated by endogenous lipid molecules. We identified CYP27, a p450 enzyme, as a link between retinoid, PPARgamma, and LXR signaling. We show that the human CYP27 gene is under coupled regulation by retinoids and ligands of PPARs via a PPAR-retinoic acid receptor response element in its promoter. Induction of the enzyme's expression results in an increased level of 27-hydroxycholesterol and upregulation of LXR-mediated processes. Upregulated CYP27 activity also leads to LXR-independent elimination of CYP27 metabolites as an alternative means of cholesterol efflux. Moreover, human macrophage-rich atherosclerotic lesions have an increased level of retinoid-, PPARgamma-, and LXR- regulated gene expression and also enhanced CYP27 levels. Our findings suggest that nuclear receptor-regulated CYP27 expression is likely to be a key integrator of retinoic acid receptor-PPARgamma-LXR signaling, relying on natural ligands and contributing to lipid metabolism in macrophages
Y1  - 2004
SN  - 0270-7306
ER  -