eprintid: 191787 rev_number: 56 eprint_status: archive userid: 608 dir: disk0/00/19/17/87 datestamp: 2010-11-08 13:19:32 lastmod: 2022-01-16 01:34:11 status_changed: 2016-07-01 15:28:43 type: article metadata_visibility: show item_issues_count: 0 creators_name: Ebner, MJ creators_name: Corol, DI creators_name: Havlikova, H creators_name: Honour, JW creators_name: Fry, JP title: Identification of neuroactive steroids and their precursors and metabolites in adult male rat brain ispublished: pub divisions: UCL divisions: B02 divisions: C08 divisions: D09 divisions: G02 divisions: D11 keywords: chromatography-mass spectrometry, different endocrine states, human female brain, GABA(A) receptors, pregnenolone sulfate, gas-chromatography, neurosteroids, progesterone, plasma, dehydroepiandrosterone note: Copyright © 2006 by The Endocrine Society. abstract: Steroids in the brain arise both from local synthesis and from peripheral sources and have a variety of effects on neuronal function. However, there is little direct chemical evidence for the range of steroids present in brain or of the pathways for their synthesis and inactivation. This information is a prerequisite for understanding the regulation and function of brain steroids. After extraction from adult male rat brain, we have fractionated free steroids and their sulfate esters and then converted them to heptafluorobutyrate or methyloxime-trimethylsilyl ether derivatives for unequivocal identification and assay by gas chromatography analysis and selected ion monitoring mass spectrometry. In the free steroid fraction, corticosterone, 3 alpha, 5 alpha-tetrahydrodeoxycorticosterone, testosterone, and dehydroepiandrosterone were found in the absence of detectable precursors usually found in endocrine glands, indicating peripheral sources and/or alternative synthetic pathways in brain. Conversely, the potent neuroactive steroid 3 alpha, 5 alpha-tetrahydroprogesterone ( allopregnanolone) was found in the presence of its precursors pregnenolone, progesterone, and 5 alpha-dihydroprogesterone. Furthermore, the presence of 3 alpha-, 11 alpha-, 17 alpha-, and 20 alpha-hydroxylated metabolites of 3 alpha, 5 alpha-tetrahydroprogesterone implicated possible inactivation pathways for this steroid. The 20 alpha-reduced metabolites could also be found for pregnenolone, progesterone, and 5 alpha-dihydroprogesterone, introducing a possible regulatory diversion from the production of 3 alpha, 5 alpha-tetrahydroprogesterone. In the steroid sulfate fraction, dehydroepiandrostrone sulfate was identified but not pregnenolone sulfate. Although pharmacologically active, identification of the latter appears to be an earlier methodological artifact, and the compound is thus of doubtful physiological significance in the adult brain. Our results provide a basis for elucidating the origins and regulation of brain steroids. date: 2006-01 publisher: ENDOCRINE SOC official_url: http://dx.doi.org/10.1210/en.2005-1065 vfaculties: VFLS oa_status: green full_text_type: other language: eng primo: open primo_central: open_green article_type_text: Article verified: verified_manual elements_source: Web of Science elements_id: 64369 doi: 10.1210/en.2005-1065 lyricists_name: Fry, Jonathan lyricists_name: Honour, John lyricists_id: JPFRY00 lyricists_id: JWHON29 full_text_status: public publication: Endocrinology volume: 147 number: 1 pagerange: 179 - 190 issn: 0013-7227 citation: Ebner, MJ; Corol, DI; Havlikova, H; Honour, JW; Fry, JP; (2006) Identification of neuroactive steroids and their precursors and metabolites in adult male rat brain. Endocrinology , 147 (1) 179 - 190. 10.1210/en.2005-1065 <https://doi.org/10.1210/en.2005-1065>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/191787/7/Fry_Endocrinology29Sep05TMP-05-02021_11.pdf