1,25-Dihydroxyvitamin D 3 downregulates the rat intestinal vitamin D 3 -25-hydroxylase CYP27A

• Published in: American journal of physiology: endocrinology and metabolism 2001-08, Vol.281 (2), p.E315-E325
• Main Authors: Theodoropoulos, Catherine, Demers, Christian, Mirshahi, Ali, Gascon-Barré, Marielle
• Format: Article
• Language: English
• ISSN: 0193-1849; 1522-1555
• DOI: 10.1152/ajpendo.2001.281.2.E315

The vitamin D 3 -25-hydroxylase CYP27A is located predominantly in liver, but its expression is also detected in extrahepatic tissues. Our aim was to evaluate the regulation of CYP27A by vitamin D 3 (D 3 ) or its metabolites in rat duodena. Vitamin D-depleted rats were repleted with D 3 , 25-hydroxyvitamin D (25OHD), or 1,25-dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ] or acutely injected 1,25(OH) 2 D 3 to investigate the mechanisms of action of the hormone. All D 3 compounds led to a progressive decrease in CYP27A mRNA, with levels after D 3 representing 20% of that observed in D depletion. 25OHD decreased CYP27A mRNA by 55%, whereas 1,25(OH) 2 D 3 led to a 40% decrease, which was accompanied by a 31% decrease in CYP27A protein levels and an 89% decrease in enzyme activity. Peak circulating 1,25(OH) 2 D 3 concentrations were, however, the highest in D 3 -repleted, followed by 25OHD- and 1,25(OH) 2 D 3 -repleted animals. 1,25(OH) 2 D 3 resulted in a decrease in both CYP27A mRNA half-life and transcription rate. Our data illustrate that the intestine expresses the D 3 -25-hydroxylase and that the gene is highly regulated in vivo through a direct action of 1,25(OH) 2 D 3 or through the local production of D 3 metabolites.