Endocrine disruptors and arterial hypertension: A developing story

Brasilina Caroccia; Ilaria Caputo; Federico Bernardo Rossi; Maria Piazza; Giorgia Pallafacchina; Gian Paolo Rossi

doi:10.1016/j.steroids.2023.109292

Endocrine disruptors and arterial hypertension: A developing story

Steroids. 2023 Nov:199:109292. doi: 10.1016/j.steroids.2023.109292. Epub 2023 Aug 6.

Authors

Brasilina Caroccia¹, Ilaria Caputo¹, Federico Bernardo Rossi¹, Maria Piazza¹, Giorgia Pallafacchina², Gian Paolo Rossi³

Affiliations

¹ Internal Emergency Medicine Unit, Department of Medicine-DIMED University of Padua, Specialized Center for Blood Pressure Disorders-Regione Veneto, 35128 Padua, Italy.
² Department of Biomedical Sciences-DSB, University of Padua, 35131 Padua, Italy; Italian National Research Council (CNR), Neuroscience Institute, 35131 Padua, Italy.
³ Internal Emergency Medicine Unit, Department of Medicine-DIMED University of Padua, Specialized Center for Blood Pressure Disorders-Regione Veneto, 35128 Padua, Italy. Electronic address: gianpaolo.rossi@unipd.it.

PMID: 37549779
DOI: 10.1016/j.steroids.2023.109292

Abstract

Endocrine disrupting Chemicals (EDCs) are substances that interfere with hormones by several mechanisms including receptor activation or antagonism, changes in gene and protein expression, modification of signal transduction, and/or epigenetic modifications in hormone-producing cells. A survey conducted by the European Union in a Northern Italian region led to the discovery of a large environmental contamination of drinking water by perfluoroalkyl substances (PFAS). As the exposed population showed a high prevalence of arterial hypertension and cardiovascular disease, we decided to investigate if PFAS could enhance the biosynthesis of aldosterone. To this aim, we exposed human adrenocortical carcinoma HAC15 cells to PFAS and found that PFAS markedly increased aldosterone synthase (CYP11B2) gene expression and aldosterone secretion. Moreover, we found that they promoted reactive oxygen species (ROS) production in mitochondria, the organelles where aldosterone biosynthesis takes place. PFAS also enhanced the effects of the aldosterone secretagogue angiotensin II (Ang II) on CYP11B2 gene expression and aldosterone secretion. We also found that not only PFAS but also polychlorinated biphenyl 126 (PCB126), a chemical compound belonging to a different category of EDCs, can increase CYP11B2 gene expression and aldosterone secretion in adrenocortical cells. This novel information needs to be considered in the context of a widespread exposure to the most common EDC, that is excess Na⁺ intake, whose detrimental effects on human health occur in the setting of aldosterone production exceeding the physiological needs and lead to high blood pressure, congestion, and cardiovascular and renal damage.

Keywords: Aldosterone; Aldosterone synthase gene expression; Arterial hypertension; Endocrine disrupting chemicals; Endocrine disruptors; Perfluoroalkyl substances; Reactive oxygen species.