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 enzymein 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 glucocorticoidsin 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.