Endocrine Abstracts

Myocardial gene expression and metabolism fluctuate over the course of the day, in association with changes in energy supply and demand. Recently, time-of-day-dependent oscillations in myocardial processes have been linked to the intrinsic cardiomyocyte circadian clock. Triiodothyronine (T₃) is an important modulator of cardiac form and function. The genomic actions of T₃ are triggered after its interaction with thyroid hormone nuclear receptors that often dimerized with RXR or RORA. Some target proteins, such as PDK4, are regulated not only by the cardiomyocyte circadian clock, but also by T₃, suggesting a potential interrelationship between the two mechanisms. Circulating levels of T₃ and its intermediates exhibit a time-of-day-dependent oscillation. However, whether the sensitivity of T₃ responsive tissues oscillate in a time-of-day-dependent manner is unknown. Thus, the purpose of the present study was to investigate whether the heart exhibits a diurnal variation in T₃ responsiveness, at a transcriptional level, and/or whether T₃ impacts the circadian clock in the heart. For this, euthyroid (C) male Wistar rats were divided in two groups: vehicle or T₃ (supraphysiological dose), administered 4 h prior each ZT. The animals were euthanized at the respective Zeitgeber Times, during 24 h. The hearts were excised and the mRNA expression was evaluated by RT-qPCR using Taqman probe specific for each target gene; cyclophilin was used as a housekeeping gene. One and two-way ANOVA analysis were used to evaluate the time-of-day-dependent differential expression for each gene/group and their interactions. In general, the administration of T₃ promoted a marked alteration in the expression of Bmal1, Pdk4 and Ucp3, revealing a time-of-day-dependent responsiveness specially at the end of the dark period for Bmal1 and throughout the whole investigated period for Pdk4 and Ucp3. Our study shows that T₃ might acts as a Zeitgeber, and alters the cardiac functions, which may help to explain some metabolic and functional disorders observed in thyroid diseases.

Disclosure: This work was supported by CAPES and FAPESP (2013/05629-4).