Differential expression of 17beta-hydroxysteroid dehydrogenases types 2 and 4 in human endometrial epithelial cell lines

Husen, Bettina; Psonka, N; Jacob-Meisel, M; Keil, Christiane; Rune, GM

doi:10.1677/jme.0.0240135

Cited by 16 publications

(7 citation statements)

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“…Detected in endometrium and endometrial epithelial cell lines [9,15]; in situ hybridization examining secretory phase endometrium only suggests mRNA present in glandular epithelium [15] Not studied Unchanged across menstrual cycle; not regulated by oestrogens or progestins in vitro [9] As for 17␤-HSD2…”

Section: Enzyme Mrna Expression Protein Expression Regulationmentioning

confidence: 99%

Oestrogen and progesterone regulation of inflammatory processes in the human endometrium

King

Critchley

2010

The Journal of Steroid Biochemistry and Molecular Biology

113

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Section: Enzyme Mrna Expression Protein Expression Regulationmentioning

confidence: 99%

Oestrogen and progesterone regulation of inflammatory processes in the human endometrium

King

Critchley

2010

The Journal of Steroid Biochemistry and Molecular Biology

113

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“…There are at least eleven human HSD17b isoenzymes expressed in a variety of tissues such as the ovary, placenta, uterus, liver, adipose tissue, prostate and testis(1). HSD17b Type 2 ( HSD17b2 ) and HSD17b Type 4 ( HSD17b4 ) are expressed in the uterus(2, 3) and control the last step in the formation of estrogens. These enzymes preferentially catalyze the conversion of estradiol (E2), the most potent and active form of estrogen, to estrone (E1), the inactive form of estrogen (4).…”

Section: Introductionmentioning

confidence: 99%

Polymorphisms in genes hydroxysteroid-dehydrogenase-17b type 2 and type 4 and endometrial cancer risk

Karageorgi

McGrath

Lee

et al. 2011

Gynecologic Oncology

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Objective-Hydroxysteroid-dehydrogenase-17b (HSD17b) genes control the last step in estrogen biosynthesis. The isoenzymes HSD17b2 and HSD17b4 in the uterus preferentially catalyze the conversion of estradiol, the most potent and active form of estrogen, to estrone, the inactive form of estrogen. Endometrial adenocarcinoma is linked to excessive exposure to estrogens. We hypothesized that single nucleotide polymorphisms (SNPs) in genes HSD17b2 and HSD17b4 may alter the enzyme activity, estradiol levels and risk of disease.Methods-Pairwise tag SNPs were selected from the HapMap Caucasian database to capture all known common (minor allele frequency>0.05) genetic variation with a correlation of at least 0.80. Forty-eight SNPs were genotyped in the case-control studies nested within the Nurses' Health Study (NHS) (cases=544, controls=1296) and the Women's Health Study (WHS) (cases=130, controls=389). The associations with endometrial cancer were examined using conditional logistic regression to estimate odds ratio and 95% confidence intervals adjusted for known risk factors. Results from the two studies were pooled using fixed effects models. We additionally investigated Correspondence to: Stalo Karageorgi, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA. Fax: +617-432-1722, skarageo@hsph.harvard.edu. Conflict of interest statementThe authors declare that there are no conflicts of interest. Author contributionsAll authors contributed to this study and approved the enclosed final manuscript. S.K. performed all analyses, assisted with study design, and prepared the manuscript; M.McG. assisted with study design, data analysis, and manuscript editing; and I.L., J.B, P.K, and I.DV. were involved in all stages of this project, including obtaining funding, study design, data collection, statistical support, and manuscript editing.Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. whether SNPs are predictive of plasma estradiol and estrone levels in the NHS using linear regression. NIH Public AccessResults-Four intronic SNPs were significantly associated with endometrial cancer risk (p-value <0.05). After adjustment for multiple testing, we did not observe any significant associations between SNPs and endometrial cancer risk or plasma hormone levels.Conclusions-This is the first study to comprehensively evaluate variation in HSD17b2 and HSD17b4 in relation to endometrial cancer risk. Our findings suggest that variation in HSD17b2 and HSD17b4 does not substantially influence the risk of endometrial cancer in Caucasians.

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“…The 17β-reduction of biologically less active E 1 is catalyzed to E 2 by 17β-HSD type 1 (6), and the oxidation of E 2 to E 1 is catalyzed by 17β-HSD type 2 (7). It was reported that 17β-HSD type 1 immunoreactivity and mRNA were absent in normal and hyperplastic endometrium and in endometrial carcinoma (8,9), and 17β-HSD type 2 expression was detected in normal endometrium (secretory phase) but was decreased in hyperplastic endometrium and endometrial carcinoma (9). This is in contrast to the results of a study of these enzymes in breast cancer, in which nearly half of the cases showed 17β-HSD type 1 immunoreactivity in carcinoma cells, whereas 17β-HSD type 2 was not expressed (10).…”

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confidence: 99%

Local Biosynthesis of Estrogen in Human Endometrial Carcinoma through Tumor-Stromal Cell Interactions

Takahashi-Shiga

Utsunomiya

Miki

et al. 2009

Clinical Cancer Research

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Purpose: The metabolism and synthesis of intratumoral estrogens are thought to play a very important role in the etiology and progression of endometrial carcinoma. Aromatase is a key enzyme in the conversion of androgens to estrogens, and aromatase localization studies have reported that aromatase immunoreactivity and mRNA were detected mainly in stromal cells. However, the effect of tumor-stromal interactions on local estrogen biosynthesis in endometrial carcinomas remains largely unknown. Experimental Design: The endometrial carcinoma cell lines (Ishikawa and RL95-2) and breast carcinoma cell line (MCF-7) were cocultured with stromal cells isolated from endometrial carcinomas, and aromatization activity was measured using liquid chromatography-tandem mass spectrometry. We then confirmed the local biosynthesis of estrogens and tumor-stromal interactions on aromatase activity in Ishikawa and RL95-2 cells. In addition, we also examined the effects of aromatase inhibitors on cell proliferation. Results: Aromatase activity was significantly higher in cocultures with Ishikawa or RL95-2 than in each monoculture, respectively. Estrone (E 1 ) concentrations were significantly higher than estradiol (E 2 ) concentrations in Ishikawa and RL95-2 cells, whereas E 2 was significantly higher than E 1 in MCF-7 cells. Cell proliferation was significantly inhibited in Ishikawa and RL95-2 cell cultures treated with aromatase inhibitors compared with control cultures. Conclusions: These results indicate the contribution of not only E 2 but also E 1 to cancer cell proliferation in endometrial carcinoma. Our study may provide important information on metabolism and synthesis of intratumoral estrogens with regard to the etiology and progression of endometrial carcinoma, thus helping to achieve improved clinical responses in patients with endometrial carcinoma, who are treated with aromatase inhibitors. (Clin Cancer Res 2009;15(19):6028-34) Endometrial carcinoma is one of the most common malignancies in developed countries, and its incidence has increased (1). In situ estrogen metabolism, including synthesis and degradation, has recently been thought to play a very important role in the development and progression of various human estrogen-dependent neoplasms. The results of several studies have shown that the concentration of estradiol (E 2 ) in endometrial carcinoma tissue was significantly higher than the concentration in normal endometrium (2). Our results from a previous study were generally consistent with those of other investigations; we found that E 2 , estrone (E 1 ), and testosterone levels in tumor tissues were several times higher than concentrations measured in serum (3). These findings indicate that intratumoral estrogen metabolism and synthesis is important in the etiology and progression of endometrial carcinoma.Intratumoral production of estrogen occurs as a result of the aromatization of androgens such as androstenedione and testosterone into estrogens, and it is catalyzed by the cytochrome P450 aromatas...

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Differential expression of 17beta-hydroxysteroid dehydrogenases types 2 and 4 in human endometrial epithelial cell lines

Cited by 16 publications

References 44 publications

Oestrogen and progesterone regulation of inflammatory processes in the human endometrium

Oestrogen and progesterone regulation of inflammatory processes in the human endometrium

Polymorphisms in genes hydroxysteroid-dehydrogenase-17b type 2 and type 4 and endometrial cancer risk

Local Biosynthesis of Estrogen in Human Endometrial Carcinoma through Tumor-Stromal Cell Interactions

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