ARS | Publication request: SYNERGISM BETWEEN 1,25-DIHYDROXYVITAMIN D3 AND 9-CIS-RETINOIC ACID IN THE REGULATION OF THE RAT RENAL 24-HYDROXYLASE

Submitted to: Vitamin D Workshop Proceedings
Publication Type: Proceedings
Publication Acceptance Date: May 29, 1997
Publication Date: N/A

Technical Abstract: The retinoic acid receptor (RXR) forms a heterodimer with the vitamin D receptor (VDR) to activate genes which are regulated by 1,25- dihydroxyvitamin D3 [1,25(OH)2D3). In the absence of RXR's ligand, 9-cis- retinoic acid (9-cis-RA), the RXR appears to be a silent partner to VDR. The effect of 9-cis-RA on VDR/RXR heterodimer formation, and 1,25(OH)2D3- mediated gene expression in vivo remains to be examined. In the present study, we examined the effect of exogenous 9-cis-RA or the 9-cis-RA precursors 9,13-di-cis-RA and 9-cis-retinaldehyde (RCHO) on 1,25(OH)2D3- mediated induction of rat renal 24-hydroxylase in vivo. Treatment groups were as follows: vehicle; 1,25(OH)2D3; 1,25(OH)2D3+9-cis-RA; 1,25(OH)2D3+9,13-di-cis-RA; 1,25(OH)2D3+9-cis-RCHO; 9-cis-RA; 9,13-di-cis- RA; and 9-cis-RCHO. 1,25(OH)2D3 was administered IP 18 h prior to sacrifice. The retinoids were administered every 4 h starting 28 h prior to sacrifice, in order to compensate for 9-cis-RA's short half-life. The last retinoid dose was administered 4 h prior to sacrifice.