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Background and purpose: The cardiovascular system is modulated by thyroid hormones and their deficiency or excess in hypo- (HY) or hyperthyroid (TH) status may affect both cardiac function and arrhythmogenesis. We hypothesized that intercellular communication via connexin-43 (Cx43) channels might be implicated. The goal of this study was to explore myocardial Cx43 and PKC expression in rats with altered thyroid status as well as the effects of antioxidant-rich red palm oil (RPO) intake. Design and Methods: Male and female 4-month-old Wistar euthyroid rats (EU); HY rats (treated with 0.05% methimazole); TH rats (treated with T3/T4, 5/25 μg/1 00g b.w./day) fed with RPO (100 microL/100gb.w./day) for six weeks were compared with untreated rats. Left ventricular tissue was taken forCx43 and PKC-epsilon mRNA and protein analysis using Real Time PCR and immunoblotting. Key Results: Heart and left ventricular weights were significantly increased in male and female TH and decreased in HY rats compared to EU rats. Cx43 mRNA level was increased in male, but not in female TH rats and decreased in HY rats regardless of sex. In contrast, Cx43 protein and its functional phosphorylated (P) forms were increased in HY, but decreased in TH rats of both sexes. PKC-epsilon gene expression did not change in male, but decreased in female TH rats whereas it increased in male, but not in female HY rats. PKC-epsilon protein expression was decreased in male, but not in female TH rats and increased in HY rats regardless of sex. RPO intake reduced heart and left ventricular weight in TH rats; partially normalized Cx43 mRNA as well as protein expression and its P forms in male and female TH and HY rats; normalized PKC-epsilon protein expression in male TH rats. In conclusion, our findings indicate sex-related differences in Cx43 and PKC-epsilon gene expression due to altered thyroid status. In general, there is a down-regulation of myocardial Cx43 and PKC-epsilon in hyperthyroidism, while up-regulation in hypothyroidism. RPO intake attenuated abnormalities of Cx43 and PKC-epsilon expression. [ABSTRACT FROM AUTHOR]