REGULATION OF SERCA-2 EXPRESSION BY THYROID-HORMONE IN CULTURED CHICK-EMBRYO CARDIOMYOCYTES

We investigated the role of thyroid hormone in the physiological perin atal increase in cardiac sarcoplasmic reticulum (SR) Ca2+ adenosinetri phosphatase (ATPase) expression. We isolated and cultured the cardiomy ocytes in 10(-8) M triiodothyronine (T-3) for 48 h and then measured S R Ca2+-ATPase mRNA and immunodetectable protein contents as well as SR -dependent Ca-45(2+) uptake rate. We also examined the effect of T-3 o n expression of the same gene in monkey kidney CV-1 cells, which do no t express thyroid hormone receptors. T-3 increased cardiomyocyte SR Ca 2+ pump mRNA content by 289 +/- 35%, and immunodetectable SR Ca2+ pump protein content by 255 +/- 44%, and SR-specific Ca-45(2+) uptake rate by 189 +/- 22% (P < 0.01 for each). In contrast, T-3 had no significa nt effect on the total cellular RNA or protein contents in the cardiom yocyte, and there was no effect of T-3 On Ca2+-ATPase mRNA content in the thyroid hormone receptor-negative CV-1 cells. These data demonstra te that T-3 increases expression of the cardiac SR Ca2+ pump, that the effect can be localized to the cardiomyocyte, and that the effect is dependent on thyroid hormone receptors. These data are consistent with pretranslational and possibly transcriptional level effect of thyroid hormone on the cardiac SR Ca2+ pump gene (SERCA 2). The gestation-ass ociated increase in thyroid hormone may be at least partially responsi ble for the previously demonstrated perinatal increase in cardiac SR C a2+ pump expression.