Cardiac Steroidogenesis—New Sites of Synthesis, or Much Ado About Nothing?

Extract

The primary adrenocortical steroids are aldosterone, synthesized in the outermost layer of cells of the adrenal cortex, the zona glomerulosa; and cortisol and corticosterone, synthesized in the next layer, or zona fasciculata. Young et al. (1) have presented data in this journal complementing other suggestions that the heart is capable of synthesizing adrenocortical steroids that have physiological or pathophysiological importance through paracrine or autocrine effects (2–6). Aldosterone produced in the zona glomerulosa is released into the circulation, to be carried to various target organs throughout the body, where it binds the mineralocorticoid receptor. This receptor, like others in the steroid receptor superfamily, acts as a transcription factor modulating the transcription of message for several proteins, many of which have not been completely characterized. Aldosterone enhances the vectorial transfer of sodium in transport epithelia (7), increases the blood pressure through its action in the brain via central sympathetic neurons, some of which alter renal function (8, 9), and promotes hypertrophy and fibrosis through direct effects on the heart and vessels (10–13). Left ventricular mass has been found to correlate with plasma aldosterone in patients with both primary aldosteronism and essential hypertension, as well as in a population-based sample (14–16), suggesting that aldosterone plays an important role in cardiac remodeling. Administration of low doses of the aldosterone receptor antagonist spironololactone in the Randomized Aldactone Evaluation Study trial in patients with congestive heart failure decreased cardiovascular related mortality by 30% and morbidity by 35% (17). This low dose of spironolactone did not affect blood pressure, suggesting a direct effect within the heart. In addition to suffering from the effects of excessive circulating aldosterone, the heart has the enzymatic machinery and the synthetic ability to produce aldosterone and other corticosteroids, which might then act in a paracrine and/or autocrine manner (1, 2–6, 18).