Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2015) 37 S4.3 | DOI: 10.1530/endoabs.37.S4.3

ECE2015 Symposia Thyroid hormone and cardiovascular system (3 abstracts)

Cardiovascular actions of novel Thyroid Hormone metabolites

Carolin Höfig

Karolinska Institutet, Stockholm, Sweden.

Thyroid hormone (TH) is one of the key players in modulating cardiovascular function. The hormone increases heart rate and force of contraction by modulating cardiac gene expression, thereby providing a molecular explanation for the clinical correlation between hyperthyroidism and cardiovascular mortality. The talk will present current aspects of cardiovascular function mediated by newly discovered TH metabolites. Recent studies have shown that a single injection of 3-iodo-L-thyronamine (3-T1AM), a decarboxylated and deiodinated TH derivative, leads to rapid decreases in heart rate and cardiac output. Although 3-T1AM is rapidly converted to several metabolites in vivo, the strong acute pharmacological responses of bradycardia and negative inotropy were solely attributed to 3-T1AM, leaving potential contributions of downstream products untested (e.g. 3-iodothyroacetic (TA1) acid or N-acetyl-3-T1AM (NAc-3-T1AM). Our studies revealed that TA1, the main degradation product of 3-T1AM, lacks any cardiovascular effects in mice, and thus constitutes an important inactivation product of 3-T1AM. However, NAc-3-T1AM, which is produced in liver and WAT from 3-T1AM, significantly increases heart rate and blood pressure in mice and directly enhances contractility of primary cardiomyocytes. Both effects are blocked by the β-adrenergic antagonist timolol maleate, demonstrating that the actions of NAc-3-T1AM on cardiomyocytes require β-adrenergic receptors. Based on our findings, we identify NAc-3-T1AM as a unique endocrine TH metabolite, providing a previously unknown link between liver, WAT and cardiovascular function.

Disclosure: This work is supported by grants from the Deutsche Forschungsgemeinschaft (HO 5096/1-1), the Karolinska Institutet’s Foundation, the Swedish Research Council and Hjärt-och Lungfonden.

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