Cited by 159Estrogen and related hormone effectsEndometrial and Cervical Cancer TreatmentsCancer, Lipids, and Metabolism

AKR1C1 and AKR1C3 may determine progesterone and estrogen ratios in endometrial cancer

Rižner, Tea Lanišnik, Šmuc, Tina, Rupreht, Ruth, Šinkovec, Jasna, Penning, Trevor M.·2006·Molecular and Cellular Endocrinology

Abstract

Endometrial cancer is the most common malignancy of the female genital tract. Its incidence correlates with prolonged estrogen stimulation unopposed by progesterone or synthetic progestins. Estrogen and progestin action is regulated at the pre-receptor level, by interconversion of active hormones (estradiol (E2), progesterone (P)) with their inactive counterparts (estrone (E1), 20alpha-hydroxyprogesterone (20alpha-OHP)) in target tissues. Expression of enzymes that control the ratio of E2 and P may thus play role in the disease process. We first confirmed that AKR1C1 (human 20alpha-hydroxysteroid dehydrogenase) in a cellular context inactivates P by forming 20alpha-OHP but does not catalyze the reverse reaction. We next examined the expression of AKR1C1 and AKR1C3 (type 5 17beta-hydroxysteroid dehydrogenase) in 16 paired specimens of endometrial cancer and adjacent normal endometrium. Quantification by isoform specific real-time PCR revealed higher expression of AKR1C1 in nine specimens and higher expression of AKR1C3 in four specimens of endometrial cancer. Importantly, upregulation of both enzymes in the same specimen was observed. Since AKR1C1 inactivates P its elevated expression in diseased endometrium may contribute to diminished protection by P, while elevated expression of AKR1C3 which forms E2 in vivo, may contribute to the enhanced estrogen action. It is suggested that the expression of AKR1C1 and AKR1C3 in endometrial cancer will govern the ratio of P:E2.

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Crossref · 10.1016/j.mce.2005.10.009

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Authors
Rižner, T. L., Šmuc, T., Rupreht, R., Šinkovec, J., & Penning, T. M.
Affiliations
  • University of Ljubljana (SI)
  • Blood Transfusion Centre of Slovenia (SI)
  • Ljubljana University Medical Centre (SI)
  • University of Pennsylvania (US)
Corresponding author
Rižner, Tea Lanišnik
Venue
Molecular and Cellular Endocrinology
Publisher
Elsevier BV
Published
2006-03
Volume
248
Issue
1-2
Pages
126-135
ISSN
0303-7207 (ISSN-L)
OpenAlex
W2032301907
Cited by
159
References
33
Citations by year
2026: 4 · 2025: 9 · 2024: 7 · 2023: 4 · 2022: 6 · 2021: 13 · 2020: 6 · 2019: 11 · 2018: 5 · 2017: 8 · 2016: 6 · 2015: 5 · 2014: 14 · 2013: 8 · 2012: 12
FWCI
2.32
Type
journal article
Language
en
Open access
closed
Locations
  • Molecular and Cellular Endocrinology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • National Cancer Institute (R01CA090744)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
  • Health Sciences › Medicine › Obstetrics and Gynecology › Endometrial and Cervical Cancer Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
Keywords
endometrial cancer, AKR1C1, AKR1C3, 20α-hydroxysteroid dehydrogenase, 17β-hydroxysteroid dehydrogenase, progesterone, estradiol, estrogen-progesterone ratio, 20alpha-dihydroprogesterone, steroid hormone metabolism, gene expression
MeSH terms
Aldo-Keto Reductase Family 1 Member C3, Animals, Endometrium, Estradiol, Estradiol Dehydrogenases, Estrogens, Female, Humans, Hydroxyprostaglandin Dehydrogenases, Isoenzymes, Oxidoreductases, Progesterone, Tumor Cells, Cultured, 17-Hydroxysteroid Dehydrogenases, 20-Hydroxysteroid Dehydrogenases, 3-Hydroxysteroid Dehydrogenases, Endometrial Neoplasms

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