Mapping Brain Aldosterone and its Biosynthesis Using Mass Spectrometry

Abstract

Aldosterone is the primary mineralocorticoid steroid produced by the zona glomerulosa layer of the adrenal cortex. The primary actions of aldosterone on the kidney are well characterized while aldosterone has significant effects in other tissues. The presence of mineralocorticoid receptors in the brain, central infusion studies, and well documented behavioral and cognitive effects of hyperaldosteronism led to speculation that the brain is also a significant target site for aldosterone. However, circulating aldosterone is actively excluded by the blood brain barrier. To better understand the role of aldosterone in the brain, novel mass spectrometry approaches were used to determine the presence and amounts of the steroid within discrete brain regions. Aldosterone concentrations were found to be markedly elevated in discrete CNS areas (hotspots) but low in others. Tracer studies with 3H-DOC showed that aldosterone is locally synthesized within the CNS at sites that likely overlap with and contribute to hotspots in the brain. The biosynthesis and actions of local CNS aldosterone represent an independent control system of relevance to salt balance, blood pressure and cognition.