Glucocorticoid hormones play vital roles in regulating diverse biological processes in health and disease. Tissue levels are regulated by enzymes which activate and inactivate hormones. The enzyme, 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1), in particular, has been identified as a potential drug target; inhibiting this enzyme attenuates glucocorticoid action by lowering local levels of active hormone. A variety of mass spectrometric approaches have been developed to characterize this enzyme in vivo. Endogenous glucocorticoids and their metabolites can be profiled in urine by GC–MS and circulating steroids are now more commonly quantified by liquid chromatography tandem mass spectrometry. Tracer dilution studies have allowed rates of generation of glucocorticoids by the enzyme to be distinguished from hormone generated directly by the adrenal glands and, in combination with arterio-venous (AV) sampling, rates of production by specific tissues have been quantified. This has allowed the contribution of liver, adipose, muscle and brain to cortisol production in metabolic disease and hence prioritized drug targets. Most recently MS imaging in combination with on-tissue derivatization has been developed to profile oxo-steroids in tissue sections, allowing molecular maps to be generated across complex tissues, where regional functions are important. The review provides a synopsis of how measurement of steroids by MS has evolved with technological advances and this has provided insight into the dynamic turnover of glucocorticoids in vivo, highlighting the milestones that have advanced the field and identifying the remaining challenges for researchers, in terms of analytical chemistry and endocrine physiology and biochemistry.
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Endoplasmic reticulumendosome contact sites. This pseudo-colored electron microscopy image shows the formation of inter-organelle membrane contact sites between late endosomes (magenta) and the endoplasmic reticulum (ER; green). This tethering results from the interaction between two ER-anchored proteins (VAP-A and VAP-B) and the late endosomeanchored protein STARD3NL. Mitochondria: brown; nucleus: blue. For further details see pp. 493-498. Image kindly provided by Fabien Alpy. - PDF Icon PDF LinkTable of Contents
Review Article|
April 11 2016
Mass spectrometry and its evolving role in assessing tissue specific steroid metabolism
Ruth Andrew;
Ruth Andrew
1
*Endocrinology, University/British Heart Foundation Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, 47, Little France Crescent, Edinburgh EH16 4TJ, U.K.
1To whom correspondence should be addressed (email Ruth.Andrew@ed.ac.uk).
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Natalie Z.M. Homer
Natalie Z.M. Homer
*Endocrinology, University/British Heart Foundation Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, 47, Little France Crescent, Edinburgh EH16 4TJ, U.K.
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Publisher: Portland Press Ltd
Received:
February 09 2016
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2016 Authors; published by Portland Press Limited
2016
Biochem Soc Trans (2016) 44 (2): 645–651.
Article history
Received:
February 09 2016
Citation
Ruth Andrew, Natalie Z.M. Homer; Mass spectrometry and its evolving role in assessing tissue specific steroid metabolism. Biochem Soc Trans 15 April 2016; 44 (2): 645–651. doi: https://doi.org/10.1042/BST20150234
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