Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2016) 41 S25.3 | DOI: 10.1530/endoabs.41.S25.3

ECE2016 Symposia What's new and exciting in nuclear receptor action? (3 abstracts)

Molecular battles between corticosteroid receptors in the heart

John Cidlowski



Heart failure is a leading cause of death in man, and stress is increasingly associated with adverse cardiac outcomes. Glucocorticoids are primary stress hormones, but their direct role in cardiovascular health and disease is poorly understood. To determine the in vivo function of glucocorticoid signaling in the heart, we generated mice with cardiomyocyte-specific deletion of the glucocorticoid receptor (GR). The cardioGRKO mice appear normal early in life but die prematurely due to spontanious heart failure. In contrast, knockout of the cardiomyocyte mineralocorticoid receptors (MR) does not lead to cardiovascular disease. To investigate whether glucocorticoid activation of cardiomyocyte MR contributes to the pathology in the cardioGRKO mice, we generated mice lacking both GR and MR in cardiomyocytes. Strikingly, the cardioGRMRKO mice are protected from the development of heart failure. These findings reveal that cardiomyocyte MR signaling, when unopposed by GR signaling, plays a major role in the progression of cardiac disease. Moreover, they suggest that combining GR agonists with MR antagonists may represent an improved therapeutic approach for treating heart disease.

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