Tandem Mass Spectrometry Imaging Reveals Distinct Accumulation Patterns of Steroid Structural Isomers in Human Adrenal Glands

Emi Takeo, Yuki Sugiura, Tatsuki Uemura, Koshiro Nishimoto, Masanori Yasuda, Eiji Sugiyama, Sumio Ohtsuki, Tatsuya Higashi, Tetsuo Nishikawa, Makoto Suematsu, Eiichiro Fukusaki, Shuichi Shimma

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)8918-8925
Number of pages8
JournalAnalytical chemistry
Volume91
Issue number14
DOIs
Publication statusPublished - 2019 Jul 16

ASJC Scopus subject areas

  • Analytical Chemistry

Fingerprint Dive into the research topics of 'Tandem Mass Spectrometry Imaging Reveals Distinct Accumulation Patterns of Steroid Structural Isomers in Human Adrenal Glands'. Together they form a unique fingerprint.

  • Cite this

    Takeo, E., Sugiura, Y., Uemura, T., Nishimoto, K., Yasuda, M., Sugiyama, E., Ohtsuki, S., Higashi, T., Nishikawa, T., Suematsu, M., Fukusaki, E., & Shimma, S. (2019). Tandem Mass Spectrometry Imaging Reveals Distinct Accumulation Patterns of Steroid Structural Isomers in Human Adrenal Glands. Analytical chemistry, 91(14), 8918-8925. https://doi.org/10.1021/acs.analchem.9b00619