Steroid sulfation in adrenal tumors

Jonathan Wolf Mueller, Nora Vogg, Thomas Alec Lightning, Isabel Weigand, Cristina Ronchi, Paul Foster, Matthias Kroiss

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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 multi-step 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 MALDI 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.
Original languageEnglish
Article numberdgab182
JournalJournal of Clinical Endocrinology and Metabolism
Volume2021
Issue number00
Early online date19 Mar 2021
DOIs
Publication statusE-pub ahead of print - 19 Mar 2021

Keywords

  • androgens/estrogens/sex hormones
  • DHEAS/DHEA-S
  • steroid disulfate/bis-sulfate
  • sulfation/sulfurylation/sulfonation

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