Allopregnanolone, pregnenolone sulfate, and epitestosterone in breast cyst fluid

Bičı́ková, Marie; Számel, I.; Hill, Martin; Tallová, Jaroslava; Stárka, L.

doi:10.1016/s0039-128x(00)00140-9

Cited by 12 publications

(5 citation statements)

References 11 publications

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“…It offers a tool to further study at molecular level the role of 17α-HSD in human, espectially for T abuse testing in sports using epiT as a control. It also permits to investigate the importance of epitestosterone in some previously reported interesting phenomenons such as its accumulation in mammary cyst fluid [25] and in human prostate [7,26], as well as its potential neuroprotective effects [27], and natural anti-androgenic effects [28]. …”

Section: Discussionmentioning

confidence: 99%

Characterization of 17α-hydroxysteroid dehydrogenase activity (17α-HSD) and its involvement in the biosynthesis of epitestosterone

et al. 2005

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BackgroundEpi-testosterone (epiT) is the 17α-epimer of testosterone. It has been found at similar level as testosterone in human biological fluids. This steroid has thus been used as a natural internal standard for assessing testosterone abuse in sports. EpiT has been also shown to accumulate in mammary cyst fluid and in human prostate. It was found to possess antiandrogenic activity as well as neuroprotective effects. So far, the exact pathway leading to the formation of epiT has not been elucidated.ResultsIn this report, we describe the isolation and characterization of the enzyme 17α-hydroxysteroid dehydrogenase. The name is given according to its most potent activity. Using cells stably expressing the enzyme, we show that 17α-HSD catalyzes efficienty the transformation of 4-androstenedione (4-dione), dehydroepiandrosterone (DHEA), 5α-androstane-3,17-dione (5α-dione) and androsterone (ADT) into their corresponding 17α-hydroxy-steroids : epiT, 5-androstene-3β,17α-diol (epi5diol), 5α-androstane-17α-ol-3-one (epiDHT) and 5α-androstane-3α,17α-diol (epi3α-diol), respectively. Similar to other members of the aldo-keto reductase family that possess the ability to reduce the keto-group into hydroxyl-group at different position on the steroid nucleus, 17α-HSD could also catalyze the transformation of DHT, 5α-dione, and 5α-pregnane-3,20-dione (DHP) into 3α-diol, ADT and 5α-pregnane-3α-ol-20-one (allopregnanolone) through its less potent 3α-HSD activity. We also have over-expressed the 17α-HSD in Escherichia coli and have purified it by affinity chromatography. The purified enzyme exhibits the same catalytic properties that have been observed with cultured HEK-293 stably transfected cells. Using quantitative Realtime-PCR to study tissue distribution of this enzyme in the mouse, we observed that it is expressed at very high levels in the kidney.ConclusionThe present study permits to clarify the biosynthesis pathway of epiT. It also offers the opportunity to study gene regulation and function of this enzyme. Further study in human will allow a better comprehension about the use of epiT in drug abuse testing; it will also help to clarify the importance of its accumulation in breast cyst fluid and prostate, as well as its potential role as natural antiandrogen.

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Section: Discussionmentioning

confidence: 99%

Characterization of 17α-hydroxysteroid dehydrogenase activity (17α-HSD) and its involvement in the biosynthesis of epitestosterone

et al. 2005

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“…Adrenal stimulation in children increased PregS parallel to cortisol levels enabling the usage of PregS in diagnosis of various adrenal and pituitary diseases in children [27,42]. A more general role of PregS became evident by reports of changed PregS levels in disease states [43,44,45,46,47]. For example, PregS serum concentrations are reduced in hypothyroidism and 7fold increase in hyperthyroidism [46].…”

Section: Pregnenolone Sulfate Levels In Serum and Tissuesmentioning

confidence: 99%

Pregnenolone Sulfate: From Steroid Metabolite to TRP Channel Ligand

Harteneck

2013

Molecules

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Pregnenolone sulfate is a steroid metabolite with a plethora of actions and functions. As a neurosteroid, pregnenolone sulfate modulates a variety of ion channels, transporters, and enzymes. Interestingly, as a sulfated steroid, pregnenolone sulfate is not the final-or waste-product of pregnenolone being sulfated via a phase II metabolism reaction and renally excreted, as one would presume from the pharmacology textbook knowledge. Pregnenolone sulfate is also the source and thereby the starting point for subsequent steroid synthesis pathways. Most recently, pregnenolone sulfate has been functionally "upgraded" from modulator of ion channels to an activating ion channel ligand. This review will focus on molecular aspects of the neurosteroid, pregnenolone sulfate, its metabolism, concentrations in serum and tissues and last not least will summarize the functional data.

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“…Pregnanolone sulfate, significantly up-regulated in breast cancer group based on our results, suggested a possible relationship between breast cancer and steroids. ( Bicikova et al, 2001 ). It was worth to mention that the sample size enrolled in this study was limited, which might lead to insufficient discovery and miss other potential biomarkers.…”

Section: Resultsmentioning

confidence: 99%

Evaluation of Untargeted Metabolomic Strategy for the Discovery of Biomarker of Breast Cancer

et al. 2022

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Discovery of disease biomarker based on untargeted metabolomics is informative for pathological mechanism studies and facilitates disease early diagnosis. Numerous of metabolomic strategies emerge due to different sample properties or experimental purposes, thus, methodological evaluation before sample analysis is essential and necessary. In this study, sample preparation, data processing procedure and metabolite identification strategy were assessed aiming at the discovery of biomarker of breast cancer. First, metabolite extraction by different solvents, as well as the necessity of vacuum-dried and re-dissolution, was investigated. The extraction efficiency was assessed based on the number of eligible components (components with MS/MS data acquired), which was more reasonable for metabolite identification. In addition, a simplified data processing procedure was proposed involving the OPLS-DA, primary screening for eligible components, and secondary screening with constraints including VIP, fold change and p value. Such procedure ensured that only differential candidates were subjected to data interpretation, which greatly reduced the data volume for database search and improved analysis efficiency. Furthermore, metabolite identification and annotation confidence were enhanced by comprehensive consideration of mass and MS/MS errors, isotope similarity, fragmentation match, and biological source confirmation. On this basis, the optimized strategy was applied for the analysis of serum samples of breast cancer, according to which the discovery of differential metabolites highly encouraged the independent biomarkers/indicators used for disease diagnosis and chemotherapy evaluation clinically. Therefore, the optimized strategy simplified the process of differential metabolite exploration, which laid a foundation for biomarker discovery and studies of disease mechanism.

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Allopregnanolone, pregnenolone sulfate, and epitestosterone in breast cyst fluid

Cited by 12 publications

References 11 publications

Characterization of 17α-hydroxysteroid dehydrogenase activity (17α-HSD) and its involvement in the biosynthesis of epitestosterone

Characterization of 17α-hydroxysteroid dehydrogenase activity (17α-HSD) and its involvement in the biosynthesis of epitestosterone

Pregnenolone Sulfate: From Steroid Metabolite to TRP Channel Ligand

Evaluation of Untargeted Metabolomic Strategy for the Discovery of Biomarker of Breast Cancer

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