Alternate steroid sulfation pathways targeted by LC-MS/MS analysis of disulfates: Application to prenatal diagnosis of steroid synthesis disorders

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dc.contributor.authorPozo, Oscar J
dc.contributor.authorMarcos, Josep
dc.contributor.authorKhymenets, Olha
dc.contributor.authorPranata, Andy
dc.contributor.authorFitzgerald, Christopher
dc.contributor.authorMcLeod, Malcolm
dc.contributor.authorShackleton, Cedric
dc.date.accessioned2019-06-21T03:59:06Z
dc.date.issued2018
dc.date.updated2019-03-24T07:19:31Z
dc.description.abstractThe steroid disulfates (aka bis-sulfates) are a significant but minor fraction of the urinary steroid metabolome that have not been widely studied because major components are not hydrolyzed by the commercial sulfatases commonly used in steroid metabolomics. In early studies, conjugate fractionation followed by hydrolysis using acidified solvent (solvolysis) was used for the indirect detection of this fraction by GC–MS. This paper describes the application of a specific LC–MS/MS method for the direct identification of disulfates in urine, and their use as markers for the prenatal diagnosis of disorders causing reduced estriol production: STSD (steroid sulfatase deficiency), SLOS (Smith-Lemli-Opitz syndrome) and PORD (P450 oxidoreductase deficiency). Disulfates were detected by monitoring a constant ion loss (CIL) from the molecular di-anion. While focused on disulfates, our methodology included an analysis of intact steroid glucuronides and monosulfates because steroidogenic disorder diagnosis usually requires an examination of the complete steroid profile. In the disorders studied, a few individual steroids (as disulfates) were found particularly informative: pregn-5-ene-3β,20S-diol, pregn-5-ene-3β,21-diol (STSD, neonatal PORD) and 5α-pregnane-3β,20S-diol (pregnancy PORD). Authentic steroid disulfates were synthesized for use in this study as aid to characterization. Tentative identification of 5ξ-pregn-7-ene-3ξ,20S-diol and 5ξ-pregn-7-ene-3ξ,17,20S-triol disulfates was also obtained in samples from SLOS affected pregnancies. Seven ratios between the detected metabolites were applied to distinguish the three selected disorders from control samples. Our results show the potential of the direct detection of steroid conjugates in the diagnosis of pathologies related with steroid biosynthesis.en_AU
dc.description.sponsorshipSpanish Health National System is acknowledged for OP contract (CPII16/00027). Strategic Plan for Research and Innovation in Health (PERIS) of the Catalan government is acknowledge for OK contract (SLT002/16/00007).en_AU
dc.format.mimetypeapplication/pdfen_AU
dc.identifier.issn0952-5041en_AU
dc.identifier.urihttp://hdl.handle.net/1885/164150
dc.language.isoen_AUen_AU
dc.publisherSociety for Endocrinologyen_AU
dc.rights© 2018 Society for Endocrinologyen_AU
dc.sourceJournal of Molecular Endocrinologyen_AU
dc.titleAlternate steroid sulfation pathways targeted by LC-MS/MS analysis of disulfates: Application to prenatal diagnosis of steroid synthesis disordersen_AU
dc.typeJournal articleen_AU
local.bibliographicCitation.issue2en_AU
local.bibliographicCitation.lastpageM12en_AU
local.bibliographicCitation.startpageM1en_AU
local.contributor.affiliationPozo, Oscar J, Fundacio Institut d'Investigacions Mediques (IMIM)en_AU
local.contributor.affiliationMarcos, Josep, Universitat Pompeu Fabraen_AU
local.contributor.affiliationKhymenets, Olha, Hospital del Maren_AU
local.contributor.affiliationPranata, Andy, College of Science, ANUen_AU
local.contributor.affiliationFitzgerald, Christopher, College of Science, ANUen_AU
local.contributor.affiliationMcLeod, Malcolm, College of Science, ANUen_AU
local.contributor.affiliationShackleton, Cedric, University of Birminghamen_AU
local.contributor.authoremailrepository.admin@anu.edu.auen_AU
local.contributor.authoruidPranata, Andy, u5078769en_AU
local.contributor.authoruidFitzgerald, Christopher, u5352327en_AU
local.contributor.authoruidMcLeod, Malcolm, u4045340en_AU
local.description.embargo2037-12-31
local.description.notesImported from ARIESen_AU
local.identifier.absfor030503 - Organic Chemical Synthesisen_AU
local.identifier.absfor110302 - Clinical Chemistry (diagnostics)en_AU
local.identifier.absfor030101 - Analytical Spectrometryen_AU
local.identifier.absseo920110 - Inherited Diseases (incl. Gene Therapy)en_AU
local.identifier.ariespublicationu4485658xPUB1377en_AU
local.identifier.citationvolume61en_AU
local.identifier.doi10.1530/JME-17-0286en_AU
local.identifier.scopusID2-s2.0-85055448258
local.identifier.uidSubmittedByu4485658en_AU
local.publisher.urlhttps://www.bioscientifica.com/en_AU
local.type.statusPublished Versionen_AU

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