Adrenal Cortical Steroidogenic Enzyme Expression is Associated with Hypertension, Obesity and Corticosteroid Use: A...

Steroidogenesis in the human adrenal cortex follows a distinct anatomical and functional zonation, which is essential for maintaining electrolyte balance, stress response, and metabolic homeostasis. Dysregulation of this tightly controlled system leads to endocrine disorders causing hypertension, such as primary aldosteronism and glucocorticoid excess. The aim of this study was to analyze the zonal distribution and expression levels of enzymes involved in steroidogenesis and correlate these findings with hypertension, body mass index and previous administration of corticosteroids while correcting severe acute respiratory syndrome coronavirus 2 infection as a potential confounder. Tissue microarrays were constructed from 99 formalin-fixed paraffin-embedded adrenal glands obtained from adult human autopsies, with clinical information on hypertension status. As controls, 14 normal adrenal glands derived from surgical specimens were included. Protein expression of CYP11B2, CYP11B1, CYP17, HSD3B1, and HSD3B2 was assessed semi-quantitatively and evaluated with respect to their localization within specific adrenal cortical zones using immunohistochemistry. The expression of CYP17, CYP11B1, CYP11B2, and HSD3B2 was inversely correlated with the presence of hypertension (p<0.001 and p=0.0149), higher body mass index (p=0.026 and p=0.001), and the administration of corticosteroids (p=0.0012, p=0.001, and p=0.002). CYP11B2 showed reduced expression in the zona glomerulosa only in the non-COVID-19 hypertension group (p=0.031). Tissue microarray-based tissue analysis is a reliable method in a research setting to detect consistent downregulation of CYP11B1, CYP11B2, and CYP17 in patients with hypertension, independent of concomitant underlying infections. The positive correlation between the body mass index and CYP11B1 expression, and the negative correlation between glucocorticoid administration and CYP11B1, may reflect clinical factors such as obesity-associated hypertension and altered aldosterone production and its relationship with metabolic syndrome.