Vitamin D Research Today is a free monthly online journal that collates and summarizes the latest research about Vitamin D, including details on sources, melanin, benefits, deficiency, supplements, calcium absorption.

Inhibition of LXRalpha signaling by vitamin D receptor: possible role of VDR in bile acid synthesis.

Jiang W, Miyamoto T, Kakizawa T, Nishio SI, Oiwa A, Takeda T, Suzuki S, Hashizume K

Department of Endocrinology, The First Clinical College, Harbin Medical University, Harbin 150001, China.

The expression of cholesterol 7alpha-hydroxylase (CYP7alpha), the rate-limiting enzyme in the catabolism of cholesterol to bile acid, is stimulated by oxysterol receptor, liver X receptor alpha (LXRalpha) and negatively regulated by a bile acid receptor, farnesoid X receptor. In the current study, we demonstrated that 1,25-(OH)(2)D3 blunted the LXRalpha-mediated induction of CYP7alpha mRNA in H4IIE rat hepatoma cells. In co-transfection experiments in HepG2 cells, VDR repressed the activity of rat CYP7alpha promoter in a ligand-dependent manner through inhibition of LXRalpha signaling. We also confirmed the ability of VDR to repress LXRalpha transcriptional activation using a synthetic LXRalpha responsive reporter. Deletion analyses revealed that the ligand-binding domain of VDR was required for the suppression and the DNA-binding domain was dispensable. Given the fact that VDR can be activated by the secondary bile acid as well as 1,25-(OH)(2)D3, the crosstalk between LXRalpha and VDR signaling in regulation of bile acid metabolism provides a possible contribution of VDR to modulate bile acid and cholesterol homeostasis, and highlights a physiological function of VDR beyond calcium metabolism in the body.

Published 31 October 2006 in Biochem Biophys Res Commun, 351(1): 176-84.
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