MSACL 2026 Abstract

Environmental Pollutants and Adrenal Steroidogenesis

Mark M Kushnir (1,2), Samira Salihovic (3), Jonas Bergquist (2,4), P. Monica Lind (5), Anders Larsson (6) and Lars Lind (6)
(1) ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, UT, (2) Department of Pathology, University of Utah, Salt Lake City, UT, (3) School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Sweden, (4) Analytical Chemistry and Neurochemistry, Uppsala University, Sweden, (5) Department of Medical Sciences, Uppsala University, Sweden, (6) Department of Medical Sciences, Uppsala University, Sweden

Mark Kushnir, PhD (Presenter) ARUP Institute for Clinical & Experimental Pathology

Presenter Bio: Mark Kushnir is Scientific Director of Mass Spectrometry R&D at ARUP Institute for Clinical and Experimental Pathology and Adjunct Professor at the Department of Pathology, University of Utah School of Medicine. Mark received PhD in Analytical Chemistry from Uppsala University (Uppsala, Sweden); his main areas of interest include development, application and clinical evaluation of novel mass spectrometry based clinical diagnostic methods for small molecule, protein and peptide biomarkers. He is author/coauthor of over 110 scientific peer reviewed publications.

Relevant Financial Disclosures (within past 24 months, reported on Jun 11, 2026) Salary ARUP Laboratories Discussing Products? NO, presenter will NOT present educational content related to products/services of the ineligible company(ies) listed above. Conflict mitigation NOT REQUIRED.

INTRODUCTION:
Cortisol (Cort) is a key steroid hormone that regulates metabolism, immunity, and stress responses. It is synthesized in the adrenal gland through a multi‑step conversion of cholesterol. Environmental contaminants (ECs) can disrupt steroid biosynthesis and regulation, thereby increasing vulnerability to pollutant‑induced endocrine effects. In this study, we investigated whether blood concentrations of four classes of ECs are associated with concentrations of five adrenal steroids (AS): cortisol and its four precursors.

METHODS:
Plasma samples from participants of the cross-sectional population-based Prospective Investigation of the Vasculature in Uppsala Seniors study (PIVUS, 70-year-old men and women, n=950) were analysed using validated mass spectrometry-based methods for four AS pregnenolone [(Pregn), 17 hydroxy Pregn (17OH-Pregn), 17 hydroxy progesterone (17OH-Prog), 11 deoxycortisol (11DC)]; 21 persistent organic pollutants (POP); 8 perfluoroalkyl substances (PFAS); 4 phthalates and 10 metals. Cortisol was measured using a commercial competitive ELISA.

RESULTS:
ECs from all four evaluated classes were associated with concentrations of AS, precursors of cortisol. The strongest associations were observed for Pregn, 17OH Pregn and 17OH Prog, all located at critical branching points of the pathway, leading to glucocorticoids, mineralocorticoids, sex hormones, and progestogens. In contrast, 11DC and cortisol showed weak associations, suggesting that upstream biosynthetic steps may be more sensitive to pollutant exposure. The most pronounced associations were observed with highly chlorinated PCBs, all analyzed phthalates, and metals: aluminum, cadmium, copper, mercury, and nickel. The weakest associations were observed with PFAS. The relationships were generally consistent between men and women, though stronger associations with Pregn, 17OH Pregn, and 17OH Prog were observed in women. Multivariable regression models identified numerous nonlinear exposure–response relationships, suggesting complex biological mechanisms. Statistically significant interaction terms among the pollutants suggest number of synergistic and antagonistic effects among the studied pollutants. Our findings suggest that chronic exposure to number of the studied ECs may disrupt the entire steroidogenic pathway. The observed association patterns suggest possible structure–activity relationships and warrant further investigation of the effects of individual pollutants and pollutant mixtures on endocrine function. The biological plausibility of the observed associations is supported by mechanisms reported in earlier studies including disruption of endocrine and metabolic pathways, such as CYP and ACTH signaling (PCBs), cholesterol transport and biotransformation (phthalates and PFAS), oxidative stress (metals), and nuclear receptor activity (PCBs, phthalates, PFAS, and metals) [1-3].

CONCLUSION:
Our findings suggest that, in older adults, multiple classes of environmental contaminants are associated with adrenal steroid concentrations. The strongest associations were observed with the upstream precursors of the pathway, indicating that the pollutants exposure may broadly influence steroid biosynthesis. Further mechanistic and epidemiological studies are needed to better understand the health implications of the pollutant’s exposure.

REFERENCES:
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