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The Analyses of 17β-Hydroxysteroid Dehydrogenase Isozymes in Human Endometrial Hyperplasia and Carcinoma1
Abstract
Intratumoral metabolism and synthesis of estrogens are considered to play very important roles in the pathogenesis and development of human endometrial adenocarcinoma. The 17beta-hydroxysteroid dehydrogenase (17beta-HSD) isozymes catalyze the interconversion of estradiol (E2) and estrone and thereby serve to modulate the tissue levels of bioactive E2. To elucidate the possible involvement of this enzyme in human endometrial carcinoma, we first examined the expression of 17beta-HSD type 1 and type 2 in 20 normal cycling human endometria, 36 endometrial hyperplasia, and 46 endometrial endometrioid adenocarcinoma using immunohistochemistry, and we then studied immunoreactivity of 17beta-HSD type 2 using immunoblotting analyses, the activity of 17beta-HSD type 1 and type 2 using thin-layer chromatography and their expression using RT-PCR in endometrial endometrioid adenocarcinoma. We correlated these findings with various clinicopathological parameters to examine the biological significance of 17beta-HSDs in human endometrial disorders. 17beta-HSD type 2 immunoreactivity in normal endometrium was present in all cases of secretory phase (n = 14), but not in any endometrial mucosa of proliferative phase (n = 6). In addition, 17beta-HSD type 2 immunoreactivity was detected in 27 of 36 (75%) endometrial hyperplasia and 17 of 46 (37%) carcinoma cases. 17beta-HSD type 1 immunoreactivity was not detected in all the cases examined. In both endometrial hyperplasia and carcinoma cases there were significant positive correlations between 17beta-HSD type 2 and progesterone receptor labeling index (LI). In carcinoma cases, a significant inverse correlation was detected between 17beta-HSD type 2 immunoreactivity and age. In addition, 17beta-HSD type 2 immunoreactivity was also correlated with 17beta-HSD type 2 enzymatic activity, and semiquantitative analyses of 17beta-HSD type 2 messenger RNA. No significant correlations were detected between 17beta-HSD type 2 and estrogen receptor LI, Ki67 LI, amount of aromatase messenger RNA or histological grade. These data indicated that the expression of 17beta-HSD type 2 in hyperplastic and/or neoplastic endometrium may represent altered cellular features through hyperplastic and neoplastic transformation. However, 17beta-HSD type 2 may also play some protective and/or suppressive roles toward unopposed estrogenic effects through inactivating E2 in situ, especially in premenopausal patients.
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“Sasano and collaborators have developed novel antibodies and reported evidence of increased immunoexpression of aromatase [81], STS [82] and 17βHSD enzymes [83] in endometrial hyperplasia and EC.”
From Endometrial Intracrinology: Oestrogens, Androgens and Endometrial Disorders (2018) · cites this paper as [83]
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“Sasano and collaborators have developed novel antibodies and reported evidence of increased immunoexpression of aromatase [81], STS [82] and 17βHSD enzymes [83] in endometrial hyperplasia and EC.”
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Metadata
- Authors
- Utsunomiya, H., Suzuki, T., Kaneko, C., Takeyama, J., Nakamura, J., Kimura, K., Yoshihama, M., Harada, N., Ito, K., Konno, R., Sato, S., Okamura, K., & Sasano, H.
- Affiliations
- Tohoku University (JP)
- Megmilk Snow Brand (Japan) (JP)
- Fujita Health University (JP)
- Corresponding author
- Utsunomiya, Hiroki
- ORCID
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2001-07
- Volume
- 86
- Issue
- 7
- Pages
- 3436-3443
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2116219667
- Cited by
- 57
- References
- 47
- Citations by year
- 2024: 1 · 2023: 1 · 2022: 1 · 2020: 2 · 2019: 1 · 2018: 5 · 2017: 3 · 2016: 2 · 2014: 2 · 2013: 2 · 2012: 3
- FWCI
- 3.46
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (11470047)
- Topics
- Health Sciences › Medicine › Obstetrics and Gynecology › Endometrial and Cervical Cancer Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
- Keywords
- 17β-hydroxysteroid dehydrogenase, endometrial hyperplasia, endometrial adenocarcinoma, endometrioid carcinoma, estrogen metabolism, estradiol, estrone, progesterone receptor, estrogen receptor, endometrial cycle
- MeSH terms
- Adenocarcinoma, Endometrial Hyperplasia, Female, Humans, Immunohistochemistry, Isoenzymes, Menstrual Cycle, Receptors, Progesterone, RNA, Messenger, 17-Hydroxysteroid Dehydrogenases, Immunoblotting, Gene Expression, Endometrial Neoplasms, Reverse Transcriptase Polymerase Chain Reaction
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