Steroid hormones are potent regulators of fuel metabolism, inflammation and stress responses. Although they circulate in the blood, their levels are fine-tuned in tissues through interconversion of active and inactive forms. These reactions are catalyzed by a series of tissue-specific enzymes e.g. 11β-hydroxysteroid dehydrogenases, aromatase, 5α-reductases. Steroid profiling by mass spectrometry is well established for matrices such and urine and plasma. This can be applied to tissue homogenates, but spatial information is lost. We have explored Matrix-Assisted Laser Desorption Ionization Mass Spectrometry Imaging (MSI) to sample directly from tissue sub-regions and hence localize steroid hormone action. Derivatization, using reagents such as Girard T, has allowed selective detection and relative quantitation of keto-steroids and oxysterols in a number of tissues, including brain, but interference can be encountered from isomers, many inactive. Ion mobility presents a potential solution, whereby isobaric species may be separated by drift time. We have evaluated a series of derivatizing reagents capable of increasing differences in collision cross-section of isomeric steroids and established <i>in silico</i> modelling approaches to predict suitable reagents. Derivatization combined with ion mobility MSI may provide a solution to visualize intracrinology at the regional level in health and disease and during drug development.<br/>

Imaging steroids in tissue by mass spectrometry: Challenges and opportunities

256th National Meeting (2018)

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