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Discovery of neurosteroid glucuronides in mouse brain |
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| Authors: | Sirkku E Kallonen Petteri Piepponen Raimo A Ketola Risto Kostiainen |
| Institution: | a Division of Pharmaceutical Chemistry, Faculty of Pharmacy, P.O. Box 56, FI-00014 University of Helsinki, Helsinki, Finland b Division of Pharmacology and Toxicology, Faculty of Pharmacy, P.O. Box 56, FI-00014 University of Helsinki, Helsinki, Finland c Centre for Drug Research, Faculty of Pharmacy, P.O. Box 56, FI-00014 University of Helsinki, Helsinki, Finland |
| Abstract: | 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. |
| Keywords: | Neuroactive steroid Neurosteroid Glucuronidation Glucuronide Liquid chromatography-mass spectrometry |
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