Discovery of neurosteroid glucuronides in mouse brain

被引：10

作者：

Kallonen, Sirkku E. ^{[2
]}

Tammimaki, Anne ^{[3
]}

Piepponen, Petteri ^{[3
]}

Raattamaa, Helena ^{[3
]}

Ketola, Raimo A. ^{[1
]}

Kostiainen, Risto ^{[2
]}

机构：

[1] Univ Helsinki, Fac Pharm, Ctr Drug Res, FI-00014 Helsinki, Finland

[2] Univ Helsinki, Fac Pharm, Div Pharmaceut Chem, FI-00014 Helsinki, Finland

[3] Univ Helsinki, Fac Pharm, Div Pharmacol & Toxicol, FI-00014 Helsinki, Finland

来源：

ANALYTICA CHIMICA ACTA | 2009年 / 651卷 / 01期

基金：

芬兰科学院;

关键词：

Neuroactive steroid; Neurosteroid; Glucuronidation; Glucuronide; Liquid chromatography-mass spectrometry; ENZYME-ASSISTED SYNTHESIS; RAT-BRAIN; MASS-SPECTROMETRY; HYDROXYSTEROID SULFOTRANSFERASES; NERVOUS-SYSTEM; IDENTIFICATION; EXPRESSION; ELECTROSPRAY; PREGNENOLONE; SULFATE;

D O I：

10.1016/j.aca.2009.07.059

中图分类号：

O65 [分析化学];

学科分类号：

070302 ; 081704 ;

摘要：

Neurosteroid glucuronides were found for the first time in brain samples. The intact glucuronides were extracted from the cortex, hippocampus, hypothalamus, and mid-brain tissues of nicotine- and water-treated mice, and detected with capillary liquid chromatography-electrospray-tandem mass spectrometry (CapLC-ESI-MS/MS). The glucuronides of estradiol, cortisol, corticosterone, tetrahydrodeoxycorticosterone, pregnenolone, and isopregnanolone were identified by comparing retention times in selected reaction monitoring (SRM) chromatograms and the relative abundances of two SRM transitions of each neurosteroid glucuronide between the reference and authentic samples, thus providing reliable identification. In vitro experiments, carried out by using S9 fractions from mouse and rat brains, showed a formation of glucuronides with selected test compounds (corticosterone, pregnenolone, and dehydroepiandrosterone), suggesting that biosynthesis of neurosteroid glucuronides is possible in rodent brain. (C) 2009 Elsevier B.V. All rights reserved.

引用

页码：69 / 74

页数：6

共 29 条

[1]

AKWA Y, 2000, CURR OPIN ENDOCRINOL, V7, P160

[2] Molecular cloning, expression and characterization of a monkey steroid UDP-glucuronosyltransferase, UGT2B19, that conjugates testosterone [J].

Bélanger, G ;

Barbier, O ;

Hum, DW ;

Bélanger, A .

EUROPEAN JOURNAL OF BIOCHEMISTRY, 1999, 260 (03) :701-708

[3] Neurosteroids:: Endogenous regulators of the GABAA receptor [J].

Belelli, D ;

Lambert, JJ .

NATURE REVIEWS NEUROSCIENCE, 2005, 6 (07) :565-575

[4] Neurosteroids in nicotine and morphine dependence [J].

Concas, A ;

Sogliano, C ;

Porcu, P ;

Marra, C ;

Brundu, A ;

Biggio, G .

PSYCHOPHARMACOLOGY, 2006, 186 (03) :281-292

[5] CHARACTERIZATION AND MEASUREMENT OF DEHYDROEPIANDROSTERONE SULFATE IN RAT-BRAIN [J].

CORPECHOT, C ;

ROBEL, P ;

AXELSON, M ;

SJOVALL, J ;

BAULIEU, EE .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1981, 78 (08) :4704-4707

[6] PREGNENOLONE AND ITS SULFATE ESTER IN THE RAT-BRAIN [J].

CORPECHOT, C ;

SYNGUELAKIS, M ;

TALHA, S ;

AXELSON, M ;

SJOVALL, J ;

VIHKO, R ;

BAULIEU, EE ;

ROBEL, P .

BRAIN RESEARCH, 1983, 270 (01) :119-125

[7] Enzyme-assisted synthesis and characterization of glucuronide conjugates of neuroactive steroids [J].

Jantti, Sirkku E. ;

Kiriazis, Alexandros ;

Reinila, Ruut R. ;

Kostiainen, Risto K. ;

Ketola, Raimo A. .

STEROIDS, 2007, 72 (03) :287-296

[8] Expression of UDP-glucuronosyltransferases (UGTs) 2B7 and 1A6 in the human brain and identification of 5-hydroxytryptamine as a substrate [J].

King, CD ;

Rios, GR ;

Assouline, JA ;

Tephly, TR .

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1999, 365 (01) :156-162

[9]

Kostiainen R, 1996, RAPID COMMUN MASS SP, V10, P1393, DOI 10.1002/(SICI)1097-0231(199608)10:11<1393::AID-RCM654>3.0.CO

[10]

2-V

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