Jonathan Wolf Mueller1,2, Nora Vogg3, Thomas Alec Lightning1, Isabel Weigand4, Cristina L Ronchi1,2,3, Paul A Foster1,2, Matthias Kroiss3,4. 1. Institute of Metabolism and Systems Research (IMSR), University of Birmingham, Birmingham, UK. 2. Centre for Endocrinology, Diabetes and Metabolism (CEDAM), Birmingham Health Partners, Birmingham, UK. 3. Department of Internal Medicine I, Division of Endocrinology and Diabetology, University Hospital Würzburg, University of Würzburg, Würzburg(Germany). 4. Department of Medicine IV, University Hospital München, Ludwig-Maximilians-Universität München, München, Germany.
Abstract
CONTEXT: The adrenal cortex produces specific steroid hormones including steroid sulfates such as dehydroepiandrosterone sulfate (DHEAS), the most abundant steroid hormone in the human circulation. Steroid sulfation involves a multistep enzyme machinery that may be impaired by inborn errors of steroid metabolism. Emerging data suggest a role of steroid sulfates in the pathophysiology of adrenal tumors and as potential biomarkers. EVIDENCE ACQUISITION: Selective literature search using "steroid," "sulfat*," "adrenal," "transport," "mass spectrometry" and related terms in different combinations. EVIDENCE SYNTHESIS: A recent study highlighted the tissue abundance of estrogen sulfates to be of prognostic impact in adrenocortical carcinoma tissue samples using matrix-assisted laser desorption ionization mass spectrometry imaging. General mechanisms of sulfate uptake, activation, and transfer to substrate steroids are reasonably well understood. Key aspects of this pathway, however, have not been investigated in detail in the adrenal; these include the regulation of substrate specificity and the secretion of sulfated steroids. Both for the adrenal and targeted peripheral tissues, steroid sulfates may have relevant biological actions beyond their cognate nuclear receptors after desulfation. Impaired steroid sulfation such as low DHEAS in Cushing adenomas is of diagnostic utility, but more comprehensive studies are lacking. In bioanalytics, the requirement of deconjugation for gas-chromatography/mass-spectrometry has precluded the study of steroid sulfates for a long time. This limitation may be overcome by liquid chromatography/tandem mass spectrometry. CONCLUSIONS: A role of steroid sulfation in the pathophysiology of adrenal tumors has been suggested and a diagnostic utility of steroid sulfates as biomarkers is likely. Recent analytical developments may target sulfated steroids specifically.
CONTEXT: The adrenal cortex produces specific steroid hormones including steroid sulfates such as dehydroepiandrosterone sulfate (DHEAS), the most abundant steroid hormone in the human circulation. Steroid sulfation involves a multistep enzyme machinery that may be impaired by inborn errors of steroid metabolism. Emerging data suggest a role of steroid sulfates in the pathophysiology of adrenal tumors and as potential biomarkers. EVIDENCE ACQUISITION: Selective literature search using "steroid," "sulfat*," "adrenal," "transport," "mass spectrometry" and related terms in different combinations. EVIDENCE SYNTHESIS: A recent study highlighted the tissue abundance of estrogen sulfates to be of prognostic impact in adrenocortical carcinoma tissue samples using matrix-assisted laser desorption ionization mass spectrometry imaging. General mechanisms of sulfate uptake, activation, and transfer to substrate steroids are reasonably well understood. Key aspects of this pathway, however, have not been investigated in detail in the adrenal; these include the regulation of substrate specificity and the secretion of sulfated steroids. Both for the adrenal and targeted peripheral tissues, steroid sulfates may have relevant biological actions beyond their cognate nuclear receptors after desulfation. Impaired steroid sulfation such as low DHEAS in Cushing adenomas is of diagnostic utility, but more comprehensive studies are lacking. In bioanalytics, the requirement of deconjugation for gas-chromatography/mass-spectrometry has precluded the study of steroid sulfates for a long time. This limitation may be overcome by liquid chromatography/tandem mass spectrometry. CONCLUSIONS: A role of steroid sulfation in the pathophysiology of adrenal tumors has been suggested and a diagnostic utility of steroid sulfates as biomarkers is likely. Recent analytical developments may target sulfated steroids specifically.
Authors: Christopher C J Fitzgerald; Rikard Hedman; Dimanthi R Uduwela; Bettina Paszerbovics; Adam J Carroll; Teresa Neeman; Adam Cawley; Lance Brooker; Malcolm D McLeod Journal: Front Mol Biosci Date: 2022-02-23