REGULATION OF CALCITRIOL RECEPTOR AND ITS MESSENGER-RNA IN NORMAL ANDRENAL-FAILURE RATS

Homologous up-regulation of calcitriol receptor (VDR) by calcitriol is believed to be a transcriptional event. In this experiment, we studie d the effect of calcitriol on VDR in normal and renal failure rats. Th e time course of the effect of calcitriol on VDR mRNA showed a biphasi c change in VDR mRNA in response to calcitriol. The concentration of i ntestinal VDR mRNA increased at six hours and reached peak levels appr oximately 15 hours after calcitriol injection. Thereafter, the mRNA be gan to decrease and by 48 hours the level had declined to below the co ntrol values. The VDR levels also increased, though they lagged behind the VDR mRNA, and nearly plateaued at 24 hours after calcitriol treat ment. In renal failure, the concentrations of VDR were lower and the l evels of VDR mRNA were higher than the respective values of normal rat s, suggesting that VDR synthesis was inhibited at post-transcriptional sites. Chronic administration of calcitriol increased the VDR but low ered the VDR mRNA levels in both normal and renal failure rats. Infusi on of uremic ultrafiltrate to normal rats resulted in lower VDR and hi gher VDR mRNA levels similar to those found in rats with renal failure . The results indicate that uremic toxins are responsible for the low VDR and high VDR mRNA in renal failure.