Androgens in cardiac hypertrophy

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In hypertensive cardiovascular diseases, estrogens and androgens have important pathophysiological effects. While estrogens seem to be mainly protective, the role of androgens is not yet well-defined. Androgens may induce or worsen hypertension and cardiac hypertrophy by different pathways. However, beneficial cardiovascular effects of androgens have also been described. Besides their well-known actions on the transcriptional activity of target genes mediated by the “classical” androgen receptor (AR), androgens also exert rapid, non-genomic effects in numerous cell types including cardiomyocytes and endothelial cells. These effects involve increases in intracellular calcium, activation of kinases such as ERK1/2, Akt, phosphorylation of mTOR, as well as the modulation of ion channels. Besides the genomic actions by the AR, the rapid effects of androgens may be a reason for sex differences in the development of myocardial hypertrophy. Results concerning the responsible receptors and the involvement of AR in the rapid actions are inconsistent. The mediating proteins are possibly different in different tissues. Since these molecular mechanisms are not yet well understood, potential therapeutic implications of the rapid androgen actions remained unexplored. Our group will further phenotypically analyse the new animal models generated in the first funding period with altered expression of AR in cardiomyocytes and endothelial cells and use them as well as suitable cell culture models to clarify the molecular mechanisms and the physiological and pathophysiological functions of rapid androgen signalling in the heart.