Mass Spectrometry Imaging for Dissecting Steroid Intracrinology within Target Tissues

Diego F. Cobice; C. Logan Mackay; Richard J. A. Goodwin; Andrew McBride; Patrick R. Langridge-Smith; Scott P. Webster; Brian R. Walker; Ruth Andrew

doi:10.1021/ac402777k

Mass Spectrometry Imaging for Dissecting Steroid Intracrinology within Target Tissues

Diego F. Cobice, C. Logan Mackay, Richard J. A. Goodwin, Andrew McBride, Patrick R. Langridge-Smith, Scott P. Webster, Brian R. Walker, Ruth Andrew^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

Steroid concentrations within tissues are modulated by intracellular enzymes. Such "steroid intracrinology" influences hormone-dependent cancers and obesity and provides targets for pharmacological inhibition. However, no high resolution methods exist to quantify steroids within target tissues. We developed mass spectrometry imaging (MSI), combining matrix assisted laser desorption ionization with on-tissue derivatization with Girard T and Fourier transform ion cyclotron resonance mass spectrometry, to quantify substrate and product (11-dehydrocorticosterone and corticosterone) of the glucocorticoid-amplifying enzyme 11 beta-HSD1. Regional steroid distribution was imaged at 150-200 mu m resolution in rat adrenal gland and mouse brain sections and confirmed with collision induced dissociation/liquid extraction surface analysis. In brains of mice with 11 beta-HSD1 deficiency or inhibition, MSI quantified changes in subregional corticosterone/11-dehydrocorticosterone ratio, distribution of inhibitor, and accumulation of the alternative 11 beta-HSD1 substrate, 7-ketocholesterol. MSI data correlated well with LC-MS/MS in whole brain homogenates. MSI with derivatization is a powerful new tool to investigate steroid biology within tissues.

Original language	English
Pages (from-to)	11576-11584
Number of pages	9
Journal	Analytical Chemistry
Volume	85
Issue number	23
DOIs	https://doi.org/10.1021/ac402777k
Publication status	Published - 3 Dec 2013

Keywords / Materials (for Non-textual outputs)

11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE-1
IN-VIVO
DERIVATIZATION
ELECTROSPRAY
MATRIX
MICE
DERIVATIVES
OXOSTEROIDS
IONIZATION
DEFICIENCY

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10.1021/ac402777k

http://pubs.acs.org/doi/abs/10.1021/ac402777k

Cite this

@article{e29f984d940a49529608318cb2dee353,

title = "Mass Spectrometry Imaging for Dissecting Steroid Intracrinology within Target Tissues",

abstract = "Steroid concentrations within tissues are modulated by intracellular enzymes. Such {"}steroid intracrinology{"} influences hormone-dependent cancers and obesity and provides targets for pharmacological inhibition. However, no high resolution methods exist to quantify steroids within target tissues. We developed mass spectrometry imaging (MSI), combining matrix assisted laser desorption ionization with on-tissue derivatization with Girard T and Fourier transform ion cyclotron resonance mass spectrometry, to quantify substrate and product (11-dehydrocorticosterone and corticosterone) of the glucocorticoid-amplifying enzyme 11 beta-HSD1. Regional steroid distribution was imaged at 150-200 mu m resolution in rat adrenal gland and mouse brain sections and confirmed with collision induced dissociation/liquid extraction surface analysis. In brains of mice with 11 beta-HSD1 deficiency or inhibition, MSI quantified changes in subregional corticosterone/11-dehydrocorticosterone ratio, distribution of inhibitor, and accumulation of the alternative 11 beta-HSD1 substrate, 7-ketocholesterol. MSI data correlated well with LC-MS/MS in whole brain homogenates. MSI with derivatization is a powerful new tool to investigate steroid biology within tissues.",

keywords = "11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE-1, IN-VIVO, DERIVATIZATION, ELECTROSPRAY, MATRIX, MICE, DERIVATIVES, OXOSTEROIDS, IONIZATION, DEFICIENCY",

author = "Cobice, {Diego F.} and Mackay, {C. Logan} and Goodwin, {Richard J. A.} and Andrew McBride and Langridge-Smith, {Patrick R.} and Webster, {Scott P.} and Walker, {Brian R.} and Ruth Andrew",

year = "2013",

month = dec,

day = "3",

doi = "10.1021/ac402777k",

language = "English",

volume = "85",

pages = "11576--11584",

journal = "Analytical Chemistry",

issn = "0003-2700",

publisher = "American Chemical Society",

number = "23",

}

TY - JOUR

T1 - Mass Spectrometry Imaging for Dissecting Steroid Intracrinology within Target Tissues

AU - Cobice, Diego F.

AU - Mackay, C. Logan

AU - Goodwin, Richard J. A.

AU - McBride, Andrew

AU - Langridge-Smith, Patrick R.

AU - Webster, Scott P.

AU - Walker, Brian R.

AU - Andrew, Ruth

PY - 2013/12/3

Y1 - 2013/12/3

N2 - Steroid concentrations within tissues are modulated by intracellular enzymes. Such "steroid intracrinology" influences hormone-dependent cancers and obesity and provides targets for pharmacological inhibition. However, no high resolution methods exist to quantify steroids within target tissues. We developed mass spectrometry imaging (MSI), combining matrix assisted laser desorption ionization with on-tissue derivatization with Girard T and Fourier transform ion cyclotron resonance mass spectrometry, to quantify substrate and product (11-dehydrocorticosterone and corticosterone) of the glucocorticoid-amplifying enzyme 11 beta-HSD1. Regional steroid distribution was imaged at 150-200 mu m resolution in rat adrenal gland and mouse brain sections and confirmed with collision induced dissociation/liquid extraction surface analysis. In brains of mice with 11 beta-HSD1 deficiency or inhibition, MSI quantified changes in subregional corticosterone/11-dehydrocorticosterone ratio, distribution of inhibitor, and accumulation of the alternative 11 beta-HSD1 substrate, 7-ketocholesterol. MSI data correlated well with LC-MS/MS in whole brain homogenates. MSI with derivatization is a powerful new tool to investigate steroid biology within tissues.

AB - Steroid concentrations within tissues are modulated by intracellular enzymes. Such "steroid intracrinology" influences hormone-dependent cancers and obesity and provides targets for pharmacological inhibition. However, no high resolution methods exist to quantify steroids within target tissues. We developed mass spectrometry imaging (MSI), combining matrix assisted laser desorption ionization with on-tissue derivatization with Girard T and Fourier transform ion cyclotron resonance mass spectrometry, to quantify substrate and product (11-dehydrocorticosterone and corticosterone) of the glucocorticoid-amplifying enzyme 11 beta-HSD1. Regional steroid distribution was imaged at 150-200 mu m resolution in rat adrenal gland and mouse brain sections and confirmed with collision induced dissociation/liquid extraction surface analysis. In brains of mice with 11 beta-HSD1 deficiency or inhibition, MSI quantified changes in subregional corticosterone/11-dehydrocorticosterone ratio, distribution of inhibitor, and accumulation of the alternative 11 beta-HSD1 substrate, 7-ketocholesterol. MSI data correlated well with LC-MS/MS in whole brain homogenates. MSI with derivatization is a powerful new tool to investigate steroid biology within tissues.

KW - 11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE-1

KW - IN-VIVO

KW - DERIVATIZATION

KW - ELECTROSPRAY

KW - MATRIX

KW - MICE

KW - DERIVATIVES

KW - OXOSTEROIDS

KW - IONIZATION

KW - DEFICIENCY

U2 - 10.1021/ac402777k

DO - 10.1021/ac402777k

M3 - Article

C2 - 24134553

SN - 0003-2700

VL - 85

SP - 11576

EP - 11584

JO - Analytical Chemistry

JF - Analytical Chemistry

IS - 23

ER -

Mass Spectrometry Imaging for Dissecting Steroid Intracrinology within Target Tissues

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Keywords / Materials (for Non-textual outputs)

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