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Characteristics of steroid hormones in systemic lupus erythematosus revealed by GC/MS-based metabolic profiling

ABSTRACT:

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with a remarkable predominance in female, suggesting that steroid hormones may be involved in the pathogenesis. Herein, more than 70 kinds of steroids in urine were detected by gas chromatography/mass spectrometry (GC/MS) to reveal SLE-specific steroid alterations. Principle component analysis demonstrated that the steroid profile was obviously distinguished between SLE patients and controls. Lower level of total androgens was observed in patients, and 9 androgens (DHEA, testosterone, Etio, androsterone, βαβ-Diol, Epi-An, Epi-DHT, 16α-OH-DHEA, A-Diol) underwent significant decrease. Besides, SLE patients exhibited slightly higher level of total estrogens than controls, and 3 estrogens (17-Epi-E3, 17α-E2, E3) were remarkably increased. Furthermore, we identified the elevation of 2 sterols (Lan, Chol), and the reduction of 1 corticoid (11-DeoxyF) and 2 progestins (5α-DHP, 11β-OH-Prog) in patients. In this study, metabolic signature of urinary steroids associated with SLE was comprehensively defined by GC/MS for the first time, and steroid metabolism disorders were found in SLE patients, especially the conversion of androgens to estrogens. Our findings will provide new insights for a deeper understanding of the mechanism of steroid hormones in the pathogenesis of SLE, and help to unravel the reason of sexual disparity in SLE.

INSTRUMENT(S): Gas Chromatography MS -

PROVIDER: MTBLS7766 | MetaboLights | 2023-07-28

REPOSITORIES: MetaboLights

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Project description:Commensal microbes are exposed to enterohepatically circulated steroids such as bile acids and hormones in the gastrointestinal, vaginal, and urinary tracts. Since commensal microbes are exposed to these molecules exclusively in association with their host, we hypothesized that they may serve as effectors to identify and characterize genetic pathways involved in the commensal-host relationship. Host specific and some ingested steroids (phytoestrogens) are enterohepatically circulated through the lumen of the small intestine. Bile acid steroids are present at high concentrations, approximating 4 to 20 mM in the duodenum, and are released in bile from the common bile duct. Steroid hormones are secreted in bile at levels approximating 6 to 13 mg per day once conjugated to glucuronide or sulfate by the liver. Re-absorption of steroids by the terminal ileum is an incomplete process: for example, 200 to 600 mg of bile acid steroids per day in humans escape to the colon where complex microbial populations exist. We have shown that steroid hormones estradiol, progesterone, and hydrocortisone serve as strong substrates for the major RND- and MFS-type (except hydrocortisone) tripartite multidrug efflux systems, AcrAB-TolC and EmrAB-TolC respectively, even though such molecules fail to demonstrate antimicrobial properties in this bacterial background (Elkins and Mullis [2006] J. Bacteriol. 188:1191-1195). Although bile acids are subject to efflux, they are also known to directly interact with intracellular global regulators such as MarR (Prouty et al. [2004] Microbiol. 150:775-783) and Rob (Rosenberg et al., [2003] Mol. Microbiol. 48:1609-1619) consequently altering antimicrobial and bile resistance profiles. In our present study, whole-genome DNA microarrays of E. coli were used to determine what general effect steroids, both bile acid and hormones, may have on the transcriptome in relation to the human commensal environment. Keywords: Comparative Chemical Class Treatment

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	Normal-13.CDF	Other

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Characteristics of steroid hormones in systemic lupus erythematosus revealed by GC/MS-based metabolic profiling

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