High levels of oxysterol sulfates in serum of patients with steroid sulfatase deficiency

Sánchez‐Guijo, Alberto; Oji, Vinzenz; Hartmann, Michaela F.; Schuppe, Hans‐Christian; Traupe, Heiko; Wudy, Stefan A.

doi:10.1194/jlr.m055608

Cited by 28 publications

(40 citation statements)

References 40 publications

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“…Interestingly, lack of STS in humans, a condition known as STS defi ciency or recessive X-linked ichthyosis (RXLI), is compatible with life. Of note, the only compounds elevated in RXLI patients, independent of their age, are 5-cholesten-3 ␤ -ol-3-sulfate [cholesterol sulfate (CS)] and oxysterol sulfates ( 4 ). High levels of CS seem to be related to the skin scaling present in most of the RXLI males ( 5 ).…”

Section: Msmentioning

confidence: 99%

“…The rest of sulfated androgens were low or not found. This same sample was measured before to profi le its levels of oxysterol sulfates, resulting in a high elevation of hydroxycholesterol sulfates ( 4 ). Figure 3 shows a comparison of the levels of CS between the samples analyzed.…”

Section: Measurement Of Sulfated Steroids In Real Samplesmentioning

confidence: 99%

“…Each IS in the mix had a concentration of 1 g/ml, with the exception of d 7 CS, which was 6 g/ml. Proteins were precipitated with 1 ml of ACN-ZnSO 4 [89 g/l, 4:1 (v/v)]. After protein precipitation, the samples were incubated again for 15 min and then centrifuged for 10 min at 14,500 g .…”

Section: Sample Preparationmentioning

confidence: 99%

“…Sample preparation was modifi ed from a previous protocol ( 4 ). Three hundred microliters of each serum or plasma sample were incubated with 50 l of IS mix during 15 min.…”

Section: Sample Preparationmentioning

confidence: 99%

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Simultaneous quantification of cholesterol sulfate, androgen sulfates, and progestagen sulfates in human serum by LC-MS/MS

Sánchez‐Guijo

Oji

Hartmann

et al. 2015

Journal of Lipid Research

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Human adrenal glands, and those of some primates, secrete high concentrations of conjugated steroids, particularly 5-androsten-3 ␤ -ol-17-one-3-sulfate [dehydroepiandrosterone sulfate (DHEAS)], which reaches different peripheral tissues through blood ( 1 ). Sulfonation increases the solubility of steroids in water-based biological fl uids such as blood or urine. Sulfated steroids, also known in the literature as steroid sulfates or steroid sulfonates, represent the most abundant fraction of steroids in human blood. Because the physiological activity has been traditionally assigned to the unconjugated steroids, the classical dogma assumes that sulfated steroids are inactive forms of steroids which require sulfate cleavage to be active . In this context, human steroid sulfatase (STS) is the enzyme that desulfates the sulfated steroids to obtain free forms. The complementary reaction, sulfonation, is provided by sulfotransferase enzymes ( Fig. 1 ). This cycle allows for the regulation and excretion of steroids.The concept of steroid sulfates as inactive compounds is under revision. A specifi c transporter for sulfated steroids in the human testis was recently described ( 2 ). Moreover, Abstract Steroids are primarily present in human fl uids in their sulfated forms. Profi ling of these compounds is important from both diagnostic and physiological points of view . Here, we present a novel method for the quantifi cation of 11 intact steroid sulfates in human serum by LC-MS/MS. The compounds analyzed in our method, some of which are quantifi ed for the fi rst time in blood, include cholesterol sulfate, pregnenolone sulfate, 17-hydroxy-pregnenolone sulfate, 16-␣ -hydroxy-dehydroepiandrosterone sulfate, dehydroepiandrosterone sulfate, androstenediol sulfate, androsterone sulfate, epiandrosterone sulfate, testosterone sulfate, epitestosterone sulfate, and dihydrotestosterone sulfate. The assay was conceived to quantify sulfated steroids in a broad range of concentrations, requiring only 300 l of serum. The method has been validated and its performance was studied at three quality controls, selected for each compound according to its physiological concentration. The assay showed good linearity (R 2 > 0.99) and recovery for all the compounds, with limits of quantifi cation ranging between 1 and 80 ng/ml. Averaged intra-day and between-day precisions (coeffi cient of variation) and accuracies (relative errors) were below 10%. The method has been successfully applied to study the sulfated steroidome in diseases such as steroid sulfatase deficiency, proving its diagnostic value. This is, to our best knowledge, the most comprehensive method available for the quantifi cation of sulfated steroids in human blood. -S á nchez-Guijo, A., V. Oji, M.

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Section: Msmentioning

confidence: 99%

Section: Measurement Of Sulfated Steroids In Real Samplesmentioning

confidence: 99%

Section: Sample Preparationmentioning

confidence: 99%

“…Sample preparation was modifi ed from a previous protocol ( 4 ). Three hundred microliters of each serum or plasma sample were incubated with 50 l of IS mix during 15 min.…”

Section: Sample Preparationmentioning

confidence: 99%

See 2 more Smart Citations

Simultaneous quantification of cholesterol sulfate, androgen sulfates, and progestagen sulfates in human serum by LC-MS/MS

Sánchez‐Guijo

Oji

Hartmann

et al. 2015

Journal of Lipid Research

Self Cite

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“…The sulfation of oxysterols is reversible and the desulfation is catalyzed by STS. Indeed, patients with STS deficiency showed increased serum levels of cholesterol sulfates and oxysterol sulfates[27]. Therefore, STS may function to enhance LXR agonist availability and reduce LXR antagonist levels, leading to the net gain of increased LXR activation.…”

Section: Discussionmentioning

confidence: 99%

Transgenic overexpression of steroid sulfatase alleviates cholestasis

Jiang

Selcer

et al. 2017

Liver Research

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Background and Aim Sulfotransferase (SULT)-mediated sulfation and steroid sulfatase (STS)-mediated desulfation represent two critical mechanisms that regulate the chemical and functional homeostasis of endogenous and exogenous molecules. STS catalyzes the hydrolysis of steroid sulfates to form hydroxysteroids. Oxygenated cholesterol derivative oxysterols are known to be endogenous ligands of the liver X receptor (LXR), a nuclear receptor with anti-cholestasis activity, whereas the sulfated oxysterols antagonize LXR signaling. The conversion of sulfated oxysterols to their non-sulfated counterparts is catalyzed by STS. The aim of this study is to determine whether STS can alleviate cholestasis by increasing the activity of LXR. Methods Liver-specific STS transgenic mice were created and subject to the lithocholic acid (LCA)-induced model of cholestasis. Results Transgenic overexpression of STS in the liver promoted bile acid elimination and alleviated LCA-induced cholestasis. The protective effect of the STS transgene was associated with the activation of LXR and induction of LXR target genes, likely because of the increased conversion of the antagonistic oxysterol sulfates to the agonistic oxysterols. Conclusions STS has a novel function in controlling the homeostasis of bile acids by regulating endogenous LXR ligands.

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Gas chromatography−mass spectrometry analysis of non‐hydrolyzed sulfated steroids by degradation product formation

Polet

Gansbeke

Albertsdóttir

et al. 2019

Drug Testing and Analysis

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Steroid detection and identification remain key issues in toxicology, drug testing, medical diagnostics, food safety control, and doping control. In this study, we evaluate the capabilities and usefulness of analyzing non‐hydrolyzed sulfated steroids with gas chromatography−mass spectrometry (GC–MS) instead of the conventionally applied liquid chromatography−mass spectrometry (LC–MS) approach. Sulfates of 31 steroids were synthesized and their MS and chromatographic behavior studied by chemical ionization−GC−triple quadrupole MS (CI−GC‐TQMS) and low energy−electron ionization−GC−quadrupole time‐of‐flight−MS (LE−EI−GC−QTOF−MS). The collected data shows that the sulfate group is cleaved off in the injection port of the GC–MS, forming two isomers. In CI, the dominant species (ie, [MH – H2SO4]+ or [MH – H4S2O8]+ for bis‐sulfates) is very abundant due to the limited amount of fragmentation, making it an ideal precursor ion for MS/MS. In LE−EI, [M – H2SO4].+ and/or [M – H2SO4 – CH3].+ are the dominant species in most cases. Based on the common GC–MS behavior of non‐hydrolyzed sulfated steroids, two applications were evaluated and compared with the conventionally applied LC–MS approach; (a) discovery of (new) sulfated steroid metabolites of mesterolone and (b) expanding anabolic androgenic steroid abuse detection windows. GC–MS and LC–MS analysis of non‐hydrolyzed sulfated steroids offered comparable sensitivities, superseding these of GC–MS after hydrolysis. For non‐hydrolyzed sulfated steroids, GC–MS offers a higher structural elucidating power and a more straightforward inclusion in screening methods than LC–MS.

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High levels of oxysterol sulfates in serum of patients with steroid sulfatase deficiency

Cited by 28 publications

References 40 publications

Simultaneous quantification of cholesterol sulfate, androgen sulfates, and progestagen sulfates in human serum by LC-MS/MS

Simultaneous quantification of cholesterol sulfate, androgen sulfates, and progestagen sulfates in human serum by LC-MS/MS

Transgenic overexpression of steroid sulfatase alleviates cholestasis

Gas chromatography−mass spectrometry analysis of non‐hydrolyzed sulfated steroids by degradation product formation

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