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

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
JournalAnalytical chemistry
DOIs
Publication statusPublished - 2019 Jan 1

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Aldosterone
Isomers
Mass spectrometry
Steroids
Imaging techniques
Steroid hormones
Tissue
Cytochrome P-450 CYP11B2
Bioactivity
Glucocorticoids
Ionization
Catecholamines
Hydrocortisone
Signal to noise ratio
Ions

ASJC Scopus subject areas

  • Analytical Chemistry

Cite this

Tandem Mass Spectrometry Imaging Reveals Distinct Accumulation Patterns of Steroid Structural Isomers in Human Adrenal Glands. / Takeo, Emi; Sugiura, Yuki; Uemura, Tatsuki; Nishimoto, Koshiro; Yasuda, Masanori; Sugiyama, Eiji; Ohtsuki, Sumio; Higashi, Tatsuya; Nishikawa, Tetsuo; Suematsu, Makoto; Fukusaki, Eiichiro; Shimma, Shuichi.

In: Analytical chemistry, 01.01.2019.

Research output: Contribution to journalArticle

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. https://doi.org/10.1021/acs.analchem.9b00619
Takeo, Emi ; Sugiura, Yuki ; Uemura, Tatsuki ; Nishimoto, Koshiro ; Yasuda, Masanori ; Sugiyama, Eiji ; Ohtsuki, Sumio ; Higashi, Tatsuya ; Nishikawa, Tetsuo ; Suematsu, Makoto ; Fukusaki, Eiichiro ; Shimma, Shuichi. / Tandem Mass Spectrometry Imaging Reveals Distinct Accumulation Patterns of Steroid Structural Isomers in Human Adrenal Glands. In: Analytical chemistry. 2019.
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