Hypothyroidism, nuclear receptors and ATP-sensitive potassium channels

CARMONA Y; GOMEZ-MEJIBA SE; RAMIREZ DC; OLIVEROS L; GIMENEZ MS

San Luis

Congreso; XLVII SAIB; 2011

Sociedad Argentina de Bioquímica y Biología Molecular

Nuclear receptors include many transcription factors that regulate the expression of specific genes that control heart metabolism. We have shown that hypothyroidism modifies heart lipid metabolism and redox balance. It is know that heart physiology depends of normal function of potassium channels. Now, we study if hypothyroidism affects the expressions both nuclear receptors and subunits of potassium channels in heart ventricle. Hypothyroid state was induced by 6-n-propyl-2-thiouracil (100mg/g body wt) in drinking water given to female Wistar rats (160 g body wt) starting 8 days before mating until day 21 of pregnancy or for 30 days in virgin rats. In heart ventricle, the protein levels of retinoic acid receptor (RARα and RARβ) were determined by Western blot, and mRNA levels of TRα, TRβ, RXRα, RXRβ and subunits of ATP-sensitive potassium channel (Kir 6.1, Kir6.2 and SUR2) by RT-PCR. Pregnancy increased the expression of RARα, RARβ, RXRβ, and Kir 6.1 and Kir 6.2 subunits, and it decreased the expression of TRα and TRβ. Hypothyroidism in pregnancy decreased RARα, RXRα, TRα and Kir 6.2 expressions, without change in RXRβ and Kir 6.1 expressions, compared with euthyroid pregnant rats. Hypothyroid virgin rats showed a decrease in RXRα, TRα, TRβ, and Kir 6.2 and SUR2 expressions. These alterations could contribute to the myocardial dysfunction that occurs during hypothyroidism.