title: Microsomal epoxide hydrolase expression in the endometrial uterine corpus is regulated by progesterone during the menstrual cycle.
abstract: We have shown previously that high expression levels of microsomal epoxide hydrolase (mEH) correlate with a poor prognosis of breast cancer patients receiving tamoxifen, suggesting that enhanced mEH expression could lead to antiestrogen resistance (Fritz et al. in J Clin Oncol 19:3-9, 2001). Thus, the purpose of this study was to gain insights into the role of mEH in hormone-responsive tissues. We analyzed biopsy samples of the endometrium by immunohistochemical staining, pointing to a regulation of mEH during the menstrual cycle: during the first half mEH expression was low, increased during the second half and reached highest levels during pregnancy. Additionally, the progesterone receptor (PR) positive human endometrial cell lines IKPRAB-36 (estrogene receptor alpha [ERalpha] negative) and ECC1-PRAB72 (ERalpha positive) were chosen to further investigate the hormonal regulation of mEH expression. Western Blot and quantitative RT-PCR analysis revealed an increase of mEH expression after treatment with medroxy-progesterone 17-acetate (MPA) in the ERalpha containing ECC1-PRAB72 cells. In contrast our results suggest that MPA had no influence on the mEH protein level in the ERalpha- IKPRAB-36 cells. In conclusion, mEH expression is regulated by progesterone in the presence of both PRs and ERalpha.
authors.affiliation: Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany.
authors.forename: Simone L
authors.initials: SL
authors.lastname: Popp
authors.forename: Ina S
authors.initials: IS
authors.lastname: Abele
authors.forename: Miriam B
authors.initials: MB
authors.lastname: Buck
authors.forename: Matthias B
authors.initials: MB
authors.lastname: Stope
authors.forename: Leen J
authors.initials: LJ
authors.lastname: Blok
authors.forename: Payman
authors.initials: P
authors.lastname: Hanifi-Moghaddam
authors.forename: Curt W
authors.initials: CW
authors.lastname: Burger
authors.forename: Peter
authors.initials: P
authors.lastname: Fritz
authors.forename: Cornelius
authors.initials: C
authors.lastname: Knabbe
mesh_terms: D015153:Blotting, Western; D018929:Cell Culture Techniques; D002460:Cell Line; D004717:Endometrium / Q000166:cytology / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology; D004851:Epoxide Hydrolases / Q000096:biosynthesis*; D047628:Estrogen Receptor alpha / Q000096:biosynthesis; D047629:Estrogen Receptor beta / Q000096:biosynthesis; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007150:Immunohistochemistry; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology; D008597:Menstrual Cycle / Q000187:drug effects / Q000502:physiology*; D011374:Progesterone / Q000502:physiology*; D011980:Receptors, Progesterone / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D011980:Receptors, Progesterone; D011374:Progesterone; D017258:Medroxyprogesterone Acetate; D004851:Epoxide Hydrolases
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