期刊
JOURNAL OF MOLECULAR ENDOCRINOLOGY
卷 61, 期 2, 页码 M1-M12出版社
BIOSCIENTIFICA LTD
DOI: 10.1530/JME-17-0286
关键词
steroid bis-sulfates; steroid disulfates; steroid sulfation; prenatal diagnosis; LC-MS/MS; steroid metabolomics
资金
- Spanish Health National System [CPII16/00027]
- Strategic Plan for Research and Innovation in Health (PERIS) of the Catalan government [SLT002/16/00007]
The 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-3 beta,20S-diol, pregn-5-ene-3 beta,21-diol (STSD, neonatal PORD) and 5 alpha-pregnane-3 beta,20S-diol (pregnancy PORD). Authentic steroid disulfates were synthesized for use in this study as aid to characterization. Tentative identification of 5 xi-pregn-7-ene-3 xi,20S-diol and 5 xi-pregn-7-ene-3 xi,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.
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