Elucidating the actions of 3-Iodothyroacetic acid in thermoregulation and cardiovascular function

Introduction: 3-Iodo-L-thyronamine (3-T₁AM) is an endogenous thyroid hormone derivative linking endocrinology, cardiovascular function and metabolism. A single injection of 3-T₁AM induces hypothermia and bradycardia within minutes upon injection. Until now, the biosynthesis of thyronamines as well as the molecular mechanisms behind the pharmacological effects are still unknown. Recently, it was shown that a single i.p. injection of 3-T₁AM in mice lead rapidly to the formation of the corresponding thyroacetic acid (TA₁); however, it is unclear if the acetic form contributes to the pharmacological effects observed after 3-T₁AM administration. This project therefore aims to determine if TA₁ plays a role in the control of thermoregulation and cardiovascular function.

Methods: To study the acute effect of a single injection of 50 mg/kg TA1, implantable radiotransmitters were used to determine heart rate and body temperature of conscious and freely moving male mice over 4 hours post-injection when compared to sham-injected as well as 3-T1AM-injected controls.

Results: Interestingly, only a slight decrease in temperature and no effect on heart rate was observed after TA₁ injection when compared to sham-injected controls, thus strikingly different from what observed after 3-T₁AM injection.

Conclusions: Our data demonstrate that TA₁ displays only minor cardiovascular or thermoregulatory activity in mice upon acute administration. The lack of hypothermia and bradycardia clearly indicates that the amino group in the ethylamine side chain is indispensable for the rapid effects of 3-T₁AM.