Increasing evidence suggests that mineralo-and glucocorticoids modulate cardiovascular homeostasis via the effects of circulating components generated within the adrenals but also through local synthesis. The aim of this study was to assess the existence of such a steroidogenic system in heart.Using the quantitative reverse transcriptase-polymerase chain reaction, the terminal enzymes of corticosterone and aldosterone synthesis (11-hydroxylase and aldosterone synthase, respectively) were detected in the rat heart. This pathway was shown to be physiologically active, since production of aldosterone, corticosterone, and their precursor, deoxycorticosterone, was detected in both the homogenate and perfusate of isolated rat hearts using radioimmunoassay after Celite column chromatography. Perfusion of angiotensin II or adrenocorticotropin for 3 h increased aldosterone and corticosterone production and decreased deoxycorticosterone, suggesting that aldosterone and corticosterone are formed within the isolated heart from a locally present substrate.Chronic regulation of this intracardiac system was then examined. As in adrenals cardiac 11-hydroxylase and aldosterone-synthase mRNAs were independently regulated by 1 week's treatment with either low sodium and high potassium diet (which increased aldosterone synthase mRNA level only), angiotensin II (which raised level of both mRNAs), or adrenocorticotropin (which stimulated the 11-hydroxylase gene exclusively). Changes in cardiac steroid levels during treatment were not directly related to their plasma levels suggesting independent regulating mechanisms. This study, therefore, provides the first evidence for the existence of an endocrine cardiac steroidogenic system in rat heart and emphasizes its potential physiological and pathological relevance.Glucocorticoids (corticosterone in the rat and cortisol in humans) and mineralocorticoids (mainly aldosterone in both species) are synthesized from cholesterol, predominantly in the adrenal cortex. The two forms of the cytochrome P-450 enzyme which catalyze the final step of these synthetic pathways are encoded by two closely related genes CYP11B1 and CYP11B2, respectively (1) but display differences in their enzymatic activity, regulation, and tissular distribution (2). P-450 11-hydroxylase (11-OHase) 1 synthesizes corticosterone from 11-deoxycorticosterone (DOC) in the zona fasciculata reticularis and is mainly regulated by adrenocorticotropic hormone (ACTH). P-450 aldosterone (Aldo)-synthase, which catalyzes synthesis of aldosterone from DOC, is present only in the zona glomerulosa. Its activity is principally controlled by angiotensin II (Ang II) and potassium and more weakly by ACTH and sodium (3, 4). While ACTH is a chronic inhibitor of aldosterone secretion, it is also a potent stimulator of its synthesis in some acute conditions (5, 6). Two other P-450c11 genes, CYP11B3 and CYP11B4 were recently cloned from a rat genomic library (7). CYP11B3 was 97% identical to CYP11B1 and encoded an enzyme with activities interm...