Abstract
Objective: To investigate the role of catechol-O-methyl transferase (COMT) in the regulation of estrogen metabolism in human endometrium. Design: Laboratory study. Setting: Academic research laboratory. Intervention(s): Immunohistochemistry was used to localize COMT protein in human endometrial tissues. Catechol-O-methyl transferase promoter-luciferace reporter gene transactivation assay was used to assess COMT promoter activity in response to estrogen and progesterone treatment in primary human endometrial stroma (pHES) cells. Catechol-O-methyl transferase protein and mRNA expression were determined by Western blot and/or real-time polymerase chain reaction. The effect of 2-methoxy estrogen treatment on DNA proliferation, B-cell lymphoma 2, and vascular epithelial growth factor protein expression were assessed by Hoechst and Western blot analyses, respectively. Main Outcome Measure(s): Catechol-O-methyl transferase protein and mRNA subcellular localization and expression in human endometrial tissues and pHES cells. Result(s): Catechol-O-methyl transferase protein expression in human endometrial tissues was up-regulated in the proliferative phase and down-regulated in the midsecretory phase of the menstrual cycle. Estrogen induced a dose-dependent increase in COMT proximal promotor-luciferace transactivation in pHES cells whereas progesterone inhibited it. Estrogen up-regulated soluble COMT protein isoform expression whereas the addition of progesterone down-regulated it in pHES cells. High doses of 2-methoxy estrogen inhibited endometrial stroma cell proliferation, and down-regulated B-cell lymphoma 2 and vascular epithelial growth factor protein expression. Conclusion(s): Catechol-O-methyl transferase expression is hormonally regulated in human endometrial stroma. Catechol-O-methyl transferase product, 2-methoxy estrogen, inhibited endometrial stroma cell proliferation and decreased vascular epithelial growth factor and B-cell lymphoma 2 protein expression.
Original language | English (US) |
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Pages (from-to) | 789-797 |
Number of pages | 9 |
Journal | Fertility and sterility |
Volume | 90 |
Issue number | 3 |
DOIs | |
State | Published - Sep 2008 |
Externally published | Yes |
Keywords
- 2-methoxy estrogen
- Catechol-O-methyl transferase
- catechol estrogen
- human endometrial stroma
ASJC Scopus subject areas
- Reproductive Medicine
- Obstetrics and Gynecology