Concentrations of estrone, estradiol and their sulfates, and evaluation of sulfatase and aromatase activities in patients with breast fibroadenoma

Pasqualini, Jörge R.; Cortés-Prieto, J; Chétrite, G.; Talbi, Mohamed; Ruiz, Andrés García

doi:10.1002/(sici)1097-0215(19970317)70:6<639::aid-ijc2>3.0.co;2-w

Cited by 98 publications

(61 citation statements)

References 23 publications

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“…The organic upper phase was collected in a new tube and evaporated to dryness. The dry residue was neutralized with 0.5 mL NaHCO 3 (50 mM) [14].…”

Section: Acid Solvolysismentioning

confidence: 99%

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Plasma estrone sulfate assay in men: Comparison of radioimmunoassay, mass spectrometry coupled to gas chromatography (GC–MS), and liquid chromatography-tandem mass spectrometry (LC-MS/MS)

Giton¹,

Caron²,

Bérubé³

et al. 2010

Clinica Chimica Acta

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, et al.. Plasma estrone sulfate assay in men: Comparison of radioimmunoassay, mass spectrometry coupled to gas chromatography (GC-MS), and liquid chromatography-tandem mass spectrometry (LC-MS/MS).: Plasma estrone sulfate assay in men: comparison between four different assay methods. Clinica Chimica Acta, Elsevier, 2010, 411 (17-18) Acknowledgments:The authors thank Dr. Noah Hardy for editing the manuscript. Methods:We simultaneously assayed estrone sulfate in the plasma of one hundred men aged 30-50 years, according to LC-MS/MS, GC-MS after solvolysis of E 1 S, radioimmunoassay after a chromatographic purification step, and a direct RIA commercial kit.Results: Estrone sulfate plasma levels obtained with the first three methods were not significantly different. However, estrone sulfate levels measured by the direct RIA were threefold higher than those obtained by the first three methods. We showed that the excessively high estrone sulfate levels obtained with the direct RIA kit had two origins:interference by high dehydroepiandrosterone sulfate plasma levels in men, and estrone sulfate inaccurate low concentrations in the standards. Conclusion:The LC-MS/MS method can be considered as an optimum option for clinical laboratory. The GC-MS method requires solvolysis to estrone, but allows simultaneous unconjugated steroid measurement. RIA method, with chromatographic purification, is cumbersome, but less expensive. DSL-5400 kit yielded estrone sulfate plasma levels that were too high.Plasma estrone sulfate assay in men: comparison between four different assay methods 3

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“…The organic upper phase was collected in a new tube and evaporated to dryness. The dry residue was neutralized with 0.5 mL NaHCO 3 (50 mM) [14].…”

Section: Acid Solvolysismentioning

confidence: 99%

“…The use of radioimmunoassay (RIA) has been well documented in the literature. For routine analysis in clinical laboratories, several authors reported RIA methods [13][14][15][16][17][18]. We described, with accuracy and precision, a specific E 1 S radioimmunoassay involving a chromatographic purification C 18 step [13].…”

Section: Introductionmentioning

confidence: 99%

Plasma estrone sulfate assay in men: Comparison of radioimmunoassay, mass spectrometry coupled to gas chromatography (GC–MS), and liquid chromatography-tandem mass spectrometry (LC-MS/MS)

Giton¹,

Caron²,

Bérubé³

et al. 2010

Clinica Chimica Acta

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“…This supposition is based on evidence that in breast parenchyma the concentrations of estrone, free and conjugated, predominate over that of estradiol. 15,16 Hence, it is a tissue in which estrone can be assumed to be the principal primary estrogen available for aromatic hydroxylation. While this study was in progress, UGT2B7 was shown to also catalyze with high efficiency the glucuronidation of all-trans retinoic acid (atRA).…”

mentioning

confidence: 99%

Expression of UGT2B7, a UDP-Glucuronosyltransferase Implicated in the Metabolism of 4-Hydroxyestrone and All-Trans Retinoic Acid, in Normal Human Breast Parenchyma and in Invasive and in Situ Breast Cancers

Gestl¹,

Green²,

Shearer³

et al. 2002

The American Journal of Pathology

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Glucuronidation, mediated by UDP-glucuronosyltransferases (UGTs), affects the actions and disposition of diverse endo-and xenobiotics. In the case of catecholestrogens (CEs), glucuronidation is likely to block their oxidation to quinone estrogens that are the putative mediators of CEs' actions as initiators of cancers. The goal of this study was to determine whether UGT2B7, the isoenzyme with a high affinity for 4-hydroxyestrone, is expressed in human breast parenchyma. Glucuronidation of 4-hydroxyestrone has relevance to breast carcinogenesis because quinone metabolites of 4-hydroxylated CEs can form potentially mutagenic depurinating DNA adducts, and because in breast tissue estrone is likely to be the predominant estrogen available for 4-hydroxylation. Using reverse transcriptase-polymerase chain reaction, immunocytochemistry, immunoblot analyses, and assays of glucuronidation of 4-hydroxyestrone, we show that UGT2B7 is expressed in human mammary epithelium, and that its expression is dramatically reduced in invasive breast cancers. In many in situ carcinomas, however, 4-hydroxyestrone immunostaining was not only preserved but even more intense than in normal mammary epithelium. The finding of reduced UGT2B7 protein and glucuronidation of 4-hydroxyestrone in invasive cancers suggests a tumor-suppressor function for the enzyme. Recent identification of all-trans retinoic acid as a substrate of UGT2B7 suggests that this function includes the generation of retinoyl-␤-glucuronide, a potent mediator of actions of retinoids important for maintaining epithelia in a differentiated state. Current knowledge does not provide any ready explanation for the apparent increase in UGT2B7 expression in carcinomas in situ. However, this finding, together with reduced immunostaining at loci showing breach of the basement membrane (microinvasion), suggests involvement of UGT2B7-catalyzed reaction(s) in protection against invasion of surrounding tissue by cancer cells.

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“…In blood, elevated levels of estrogen were associated with the increased risk for breast cancer in both pre-and postmenopausal women (46,47). Furthermore, higher concentrations of estrogen were found in breast tumor tissue compared to normal breast tissue (48)(49)(50). Approximately two-thirds of all breast cancer patients were positive for ER, and could benefit from hormone therapy, but up to 50% of these cases had either de novo resistance or developed resistance during treatment (51,52).…”

Section: Estrogen and Breast Cancermentioning

confidence: 99%

Hormonal regulation of immune modulators in human breast tissue

Morad¹

2015

Linköping University Medical Dissertations

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Breast cancer is the most common form of cancer and the second leading cause of malignancy-associated death in women worldwide. Estrogens are the main sex hormones in women. They are essential for the development and function of normal breast mammary glands; however, prolonged exposure to estrogens increases the risk of breast cancer development and progression. Approximately two-thirds of all breast cancer patients are positive for estrogen receptor (ER), but only 50% of those cases can benefit from antiestrogen therapy. In this thesis we investigated the effects of estrogen, diet modification, and anti-estrogen drugs on several immune modulators in normal human breast tissue. We used the microdialysis technique to sample the immune modulators in situ in normal human breast tissue, in malignant breast tissue, and in tumor tissue from both the immune competent mice with murine breast cancer and immune deficient mice bearing human breast tumors. Furthermore, we also used ex vivo culture of normal breast tissue and in vitro cell culture of breast cancer cell lines. A combined cell culture (co-culture) of breast cancer cell lines, together with the primary mature adipocytes, was also used in this thesis. In Paper I and Paper II, our results suggested that estrogen exerted both proinflammatory and pro-tumorigenic effects in normal human breast tissue. Estradiol increased extracellular interleukin-1β (IL-1β) and leptin levels and decreased IL-1Ra and adiponectin levels in normal human breast tissue. In contrast, tamoxifen decreased IL-1β and leptin levels and increased IL-1Ra and adiponectin levels, shifting the environment towards an antiinflammatory and antitumorigenic state. Diet modification with flaxseed for 30 days also increased IL-1Ra levels, creating an anti-inflammatory environment in normal breast tissue. In the breast cancer tissue, we found that extracellular IL-1β levels and leptin levels were significantly higher, whereas adiponectin levels were significantly lower, compared with normal adjacent breast tissue, which suggested a more proinflammatory state. In the third paper, our in vivo investigation of normal breast tissue revealed significant correlations between vascular endothelial growth factor (VEGF) and leptin, IL-1β and leptin, and between VEGF and IL-1β. No correlations were found in the abdominal subcutaneous (s.c.) fat tissue. Our in vitro inhibition experiments suggested that VEGF was a potent regulator of leptin, but that leptin was not a potent regulator of VEGF. Co-culture per se altered the release of VEGF and leptin and enhanced the effects of estradiol, compared with monocultures of the included cell types. In conclusion, the results presented in this thesis will increase the overall understanding of the role of estrogens in breast cancer, which may be useful in future treatment studies

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Concentrations of estrone, estradiol and their sulfates, and evaluation of sulfatase and aromatase activities in patients with breast fibroadenoma

Cited by 98 publications

References 23 publications

Plasma estrone sulfate assay in men: Comparison of radioimmunoassay, mass spectrometry coupled to gas chromatography (GC–MS), and liquid chromatography-tandem mass spectrometry (LC-MS/MS)

Plasma estrone sulfate assay in men: Comparison of radioimmunoassay, mass spectrometry coupled to gas chromatography (GC–MS), and liquid chromatography-tandem mass spectrometry (LC-MS/MS)

Expression of UGT2B7, a UDP-Glucuronosyltransferase Implicated in the Metabolism of 4-Hydroxyestrone and All-Trans Retinoic Acid, in Normal Human Breast Parenchyma and in Invasive and in Situ Breast Cancers

Hormonal regulation of immune modulators in human breast tissue

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