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

Retinoid X receptor-gamma (RXRgamma) 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 RXRgamma or whether all- trans -retinoic acid (tRA) and thyroid hormone (T3) could influence RXRgamma transcript levels in these cells. First, in situ hybridization experiments were used to test for any spatio-temporal correlation between RXRgamma gene expression and the previously shown requirement for retinoid signalling in embryonic ventricular cardiomyocytes. It was shown that RXRgamma 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 RXRgamma transcript levels between neonatal and adult heart. We show that levels of two RXRgamma 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 RXRgamma transcripts, making them a novel in vitro system for the study of RXRgamma gene regulation in heart-derived cells. Finally, this system was used to examine whether tRA and T3can influence levels of RXRgamma transcripts because they have been shown to have antagonistic effects in this system and to influence RXRgamma RNA levels in other systems. It was shown by Northern blot experiments, that in this system, RXRgamma transcript levels are differentially influenced by these two hormones. The significance of these findings in relation to previously published work is discussed.