Primary
aldosteronism (PA) is a disease characterized by high
aldosterone levels caused by benign adrenal
tumors being the most frequent cause of secondary
hypertension.
Aldosterone plays vital physiological roles through the
mineralocorticoid receptor (MR) but in certain cell types, it can also activate the
glucocorticoid (GC) receptor (GR). Both MR and GR are structurally and functionally related and belong to the same family of
ligand-dependent
transcription factors that recognize identical GC regulatory elements (GREs) on their target genes. GCs play key roles in skin pathophysiology acting through both GR and MR; however, the effects of
aldosterone and the potential association of PA and
skin disease were not previously addressed. Skin samples from PA revealed histopathological alterations relative to control subjects, featuring epidermal
hyperplasia, impaired differentiation, and increased dermal infiltrates, correlating with increased NF-κB signaling and up-regulation of TNF-A and
IL-6 cytokines. PA skin samples also showed significantly higher expression of MR, GR, and HSD11B2. In cultured keratinocytes,
aldosterone treatment increased GRE transcriptional activity which was significantly inhibited by co-treatment with GR- and MR-antagonists. This study demonstrates that high levels of
aldosterone in PA patients correlate with skin anomalies and inflammatory features associated with abnormal GR/MR activation in epidermal keratinocytes.