Tandem Mass Spectrometry Imaging Reveals Distinct Accumulation Patterns of Steroid Structural Isomers in Human Adrenal Glands
journal contributionposted on 16.06.2019, 00:00 by Emi Takeo, Yuki Sugiura, Tatsuki Uemura, Koshiro Nishimoto, Masanori Yasuda, Eiji Sugiyama, Sumio Ohtsuki, Tatsuya Higashi, Tetsuo Nishikawa, Makoto Suematsu, Eiichiro Fukusaki, Shuichi Shimma
Visualizing tissue distribution of steroid hormones is a promising application of MALDI mass spectrometry imaging (MSI). On-tissue chemical derivatization using Girard’s T reagent has enhanced the ionization efficiency of steroids. However, discriminating between structural isomers with distinct bioactivities remains a challenge. Herein, we used ion trap MS/tandem MS (MS3) to distinguish a mineralcorticoid aldosterone (Aldo) and a glucocorticoid cortisol (F), from their structural isomers. Our method is also useful to detect hybrid steroids (18-hydroxycortisol [18-OHF] and 18-oxocortisol) with sufficient signal-to-noise ratio. The clinical applicability of the tandem MS method was evaluated by analyzing F, Aldo, and 18-OHF distributions in human adrenal glands. In such clinical specimens, small Aldo-producing cell clusters (APCCs) were identified and were first found to produce a high level of Aldo and not to contain F. Moreover, a part of APCCs produced 18-OHF, presumably converted from F by APCC-specific CYP11B2 activity. Catecholamine species were also visualized with another derivatization reagent (TAHS), and those profiling successfully discriminated pheochromocytoma species. These tandem MSI-methods, coupled with on-tissue chemical derivatization has proven to be useful for detecting low-abundance steroids, including Aldo and hybrid steroids and thus identifying steroid hormone-producing lesions.
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low-abundance steroidsDistinct Accumulation Patternsglucocorticoid cortisolderivatization reagentCatecholamine speciesisomersSteroid Structural IsomersHuman Adrenal Glands Visualizing tissue distribution18- OHF distributions18- OHFAldo-producing cell clusters18- oxocortisolMS 3mineralcorticoid aldosteroneon-tissue chemical derivatizationOn-tissue chemical derivatizationMALDI mass spectrometry imagingTAHStandem Mass Spectrometry Imagingionization efficiencytandem MS methodtandem MSI-methodsAPCC-specific CYP 11B activitypheochromocytoma specieshormone-producing lesions