Endocrine Abstracts

Both metabolism and cardiac function fluctuate over the course of the day according to energy supply and demand. The triiodothyronine (T₃) regulates several genes related to metabolism and function in cardiomyocytes. Our previous data have suggested that there is a potential interrelationship between the regulation of cardiac function by T₃ and the intrinsic circadian clock in the heart. Considering that: i) the hypothyroidism is associated to a reduction on cardiac function, presenting lower frequency and duration of ventricular contraction and, ii) the oscillation in the circulating levels of T₃ during the 24 h are changed in this pathological condition, the purpose of the present study was to investigate the expression of clock genes and clock-controlled genes related to the cardiac metabolism and contraction in hypothyroid adult animals. For this, euthyroid and thyroidectomized male Wistar rats were euthanized every 3 h during 24 h. The hearts were excised and the mRNA expression was evaluated by RT-qPCR using cyclophilin as a housekeeping gene. One and two-way ANOVA, as well as, Cosinor analysis were used to evaluate the time-of-day-dependent differential expression for each gene/group and their interactions. In general, the hypothyroidism reduced the expression of Pdk4, at dark phase – ZT15, and Ucp3, at light phase – ZT2 and 9. No significant changes were noticed in Bmal1, Per2, Dbp and Rora expression throughout the whole investigated period. Our study shows that in the hypothyroidism there are punctual changes in the content of transcripts related to the cardiac metabolism and function but the expression of core-clock genes are preserved. These results corroborate with our previous investigation showing that T₃ actions in the heart seem to be independent of the clock, acting in specific target pathways like pyruvate dehydrogenase kinase and mitochondrial electron transport chain, which in turn can alter heart metabolism and function.