Regulation of retinoid X receptor-γ gene transcript levels in rat heart cells

Abstract

Retinoid X receptor-γ (RXRγ) is a transcription factor that mediates retinoid signalling and is expressed in rat heart during adult life. However, its expression in embryonic and neonatal heart has not been investigated and it is not known whether ventricular cardiomyocytes express RXRγ or whether all-trans-retinoic acid (tRA) and thyroid hormone (T3) could influence RXRγ transcript levels in these cells. First, in situ hybridization experiments were used to test for any spatio-temporal correlation between RXRγ gene expression and the previously shown requirement for retinoid signalling in embryonic ventricular cardiomyocytes. It was shown that RXRγ transcripts are not detectable in embryonic heart at all developmental stages examined under conditions where they are detectable in other embryonic tissues. Second, Northern blotting was used to examine whether there is a difference in RXRγ transcript levels between neonatal and adult heart. We show that levels of two RXRγ transcripts are developmentally regulated during the postnatal period because they differ between neonatal and adult hearts. Third, it was demonstrated that primary cultures of neonatal rat ventricular cardiomyocytes express RXRγ transcripts, making them a novel in vitro system for the study of RXRγ gene regulation in heart-derived cells. Finally, this system was used to examine whether tRA and T3 can influence levels of RXRγ transcripts because they have been shown to have antagonistic effects in this system and to influence RXRγ RNA levels in other systems. It was shown by Northern blot experiments, that in this system, RXRγ transcript levels are differentially influenced by these two hormones. The significance of these findings in relation to previously published work is discussed.