Expression and cyclic variations of catechol-O-methyl transferase in human endometrial stroma.
OBJECTIVE
To investigate the role of catechol-O-methyl transferase (COMT) in the regulation of estrogen metabolism in human endometrium.


METHODS
Laboratory study.


METHODS
Academic research laboratory.


METHODS
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.


METHODS
Catechol-O-methyl transferase protein and mRNA subcellular localization and expression in human endometrial tissues and pHES cells.


RESULTS
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.


CONCLUSIONS
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.
Salih
Sana M
SM
Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Texas, USA.
Salama
Salama A
SA
Fadl
Amin A
AA
Nagamani
Manubai
M
Al-Hendy
Ayman
A
D000328:Adult; D002394:Catechol O-Methyltransferase / Q000378:metabolism*; D002478:Cells, Cultured; D004717:Endometrium / Q000378:metabolism*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D006801:Humans; D008597:Menstrual Cycle / Q000378:metabolism*; D008875:Middle Aged; D017154:Stromal Cells / Q000378:metabolism
D002394:Catechol O-Methyltransferase