Context: Primary aldosteronism (PAL) is the most frequent cause of secondary arterial hypertension. In PAL, aldosterone production is chronic, excessive and autonomous.

Objective: To identify the angiotensin-II independent alterations of steroidogenesis responsible for PAL.

Design: Genome wide gene expression was compared in two tissues differentiated for aldosterone production, both non stimulated by circulating angiotensin II and differing for their autonomy to produce aldosterone: aldosterone-producing adenoma (APA) and its adjacent dissected zona glomerulosa (ZG).

Setting: The "Comete" Network

Patients: Patients with APA.

Intervention: Transcriptome comparison of one APA and its adjacent ZG by SAGE; validation by in situ hybridization for 19 genes in 11 samples.

Outcome: Genes differentially expressed in APA and adjacent ZG.

Results: Activation of steroidogenesis in PAL is restricted to the overexpression of the enzymes producing aldosterone-specific steroids, aldosterone synthase and also 21-hydroxylase, suggesting that upstream precursors production is not limiting. Increased expression of HDL receptor, adrenodoxin and P450 oxidoreductase suggests that these systems provide cholesterol and electrons to the mitochondrial steroidogenic enzymes. As for acute stimulation of aldosterone production, an activation of calcium signaling is suggested by concordant overexpression of calcium-binding proteins or effectors. Calcium activation may result from an abnormal activity of Gq-protein coupled receptors. This calcium activation may be the starting point of the other gene expression changes observed in APA. Finally, other differentially expressed genes include 3 genes encoding unidentified proteins.

Conclusion: This work provides an original and integrated view of the mechanisms of aldosterone production in PAL.