Hormonal regulation of catechol-O-methyl transferase activity in women with uterine leiomyomas

Salama, Salama A.; Ho, Shu Leong; Wang, Hui Qun; Tenhunen, Jukka; Tilgmann, Carola; Al-Hendy, Ayman

doi:10.1016/j.fertnstert.2005.12.049

Cited by 36 publications

(43 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The estrogen mediated upregulation of S-COMT expression in pHES cells in this study was similar to the effect of estrogen on COMT expression in hamster kidney cells where subchronic estrogen treatment increased COMT immunostaining (20). It contrasted, however, with the effects of estrogen on S-COMT expression in MCF-7 and in human myometrial cells where estrogen treatment down-regulated S-COMT expression levels (13,21,22). The variable cell-type specific response of S-COMT expression to estrogen is likely because of the presence of different levels of estrogen receptor isoforms as well as different receptor coactivators and corepressors in different cell types (23,24).…”

Section: Author Manuscript Author Manuscriptmentioning

confidence: 96%

Expression and cyclic variations of catechol-O-methyl transferase in human endometrial stroma

Salih

Salama

Fadl

et al. 2008

Fertility and Sterility

Self Cite

View full text Add to dashboard Cite

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, Bcell 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 promotorluciferace 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. HHS Public Access Author Manuscript Author ManuscriptAuthor Manuscript Author ManuscriptConclusion(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. KeywordsCatechol-O-methyl transferase; human endometrial stroma; catechol estrogen; 2-methoxy estrogenThe human endometrium is a metabolically active tissue that undergoes monthly cell proliferation, differentiation, and apoptosis during the female reproductive cycle. The molecular mechanisms that control synchronized endometrial development during each menstrual cycle are still poorly understood. Estrogen and progesterone are known to modulate the endometrium in a variety of ways. Estrogen stimulates endometrial cell proliferation whereas progesterone induces endometrial cell decidualization and prepares the endometrium for blastocyst implantation. Genes that are modified by estrogen and/or progesterone are likely to be important players in the monthly cyclic development of the endometrium and possible culprits in the pathogenesis of endometrial disorders. Catechol-Omethyl transferase (COMT) is an enzyme that catalyses O-methylation and inactivation of a variety of metabo...

show abstract

Section: Author Manuscript Author Manuscriptmentioning

confidence: 96%

Expression and cyclic variations of catechol-O-methyl transferase in human endometrial stroma

Salih

Salama

Fadl

et al. 2008

Fertility and Sterility

Self Cite

View full text Add to dashboard Cite

show abstract

“…Our previous work indicated that the COMT promoter regions harbor multiple progesterone half-site response elements [30], suggesting that progesterone/progesterone receptors are among those transcription factors involved in the regulation of COMT expression in breast cells. Our data clearly indicated that progesterone downregulates COMT expression at the transcriptional level.…”

Section: Discussionmentioning

confidence: 99%

“…Quantitative real time reverse transcription-polymerase chain reaction (RT-PCR) was performed in triplicate for each sample on an ABI Prism 7900HT with TaqMan universal PCR master mix (Applied Biosystems, Foster City, CA), as previously described [30]. For each sample, the ΔCt values were determined by subtracting the average of triplicate Ct values of the target gene from the average of the triplicate Ct values of the reference gene (glyseraldehyde-3-phosphate dehydrogenase, GAPDH).…”

Section: Rna Isolation and Real Time Reverse Transcription-polymerasementioning

confidence: 99%

“…Since COMT plays a critical role in the detoxification of carcinogenic estrogen metabolites, studying the transcription regulation of COMT expression is of particular interest in the understanding of the pathobiology of estrogen-related cancer and in designing chemopreventive strategies. Previous work from our laboratory and from other groups indicates that the expression of COMT is regulated by sex steroid hormones [29][30][31]. The current study was undertaken to systematically investigate the potential role of progesterone/progesterone receptors in the regulation of COMT gene expression in breast cancer cell lines.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Progesterone regulates catechol-O-methyl transferase gene expression in breast cancer cells: Distinct effect of progesterone receptor isoforms

Salama

Jamaluddin

Kumar

et al. 2007

The Journal of Steroid Biochemistry and Molecular Biology

Self Cite

View full text Add to dashboard Cite

There is strong evidence that catechol-O-methyl transferase (COMT) protects breast cells against estrogen-induced cancer by detoxifying catecholestrogens, the carcinogenic estrogen metabolites. COMT gene expression is controlled by two promoters-a proximal promoter (COMTP1) and a distal promoter (COMTP2)-that regulate the expression of soluble (S-COMT) and membranebound (MB-COMT) isoforms, respectively. We investigated the transcriptional regulation of the COMT gene by progesterone/progesterone receptors in breast cancer cells. Our results indicated that progesterone (P4) downregulates COMT gene expression in breast cancer cell lines. In addition, the COMTP1 and COMTP2 harbor several progesterone response elements (PREs). Electrophoretic mobility shift assay (EMSA) indicated that nuclear extracts of T47D cells bind to the identified PREs in COMTP1. Site-directed mutagenesis of PREs in COMTP1 not only reversed the P4-induced inhibition of COMTP1, but also increased its basal activity. The two progesterone receptor isoforms, PR-A and PR-B, were found to have opposite effects on the regulation of P4 in COMT expression; PR-A is associated with P4-induced upregulation of COMT, while PR-B is associated with P4-induced downregulation of COMT. In summary, our data demonstrated that P4 downregulates the COMT gene expression through multiple PREs in the COMT promoters and that different progesterone receptor isoforms have distinctive effects on COMT gene expression.

show abstract

“…Increased COMT activity is associated with increased estrogen levels and increased uterine fibroid growth. It has been reported that COMT expression is higher in uterine fibroid than in normal myometrium [42]. COMT inhibitor can potentially suppress estrogen synthesis and decrease uterine fibroid growth.…”

Section: Catechol-o-methyltransferase Inhibitormentioning

confidence: 97%

Medical Management of Uterine Fibroids

Parsanezhad

Jahromi

2012

Curr Obstet Gynecol Rep

View full text Add to dashboard Cite

Uterine leiomyomas are the most common benign tumors of the uterus. Though benign, they can affect the quality of life for many women. Compared with the standard surgical treatments, medical therapy is attractive and avoids possible surgery-related complications. No medical therapy currently exists that can induce rapid regression of the myoma and symptoms with minimal side effects without affecting fertility. This review evaluates medical treatments that are currently available for the treatment of uterine fibroids.

show abstract

Hormonal regulation of catechol-O-methyl transferase activity in women with uterine leiomyomas

Cited by 36 publications

References 17 publications

Expression and cyclic variations of catechol-O-methyl transferase in human endometrial stroma

Expression and cyclic variations of catechol-O-methyl transferase in human endometrial stroma

Progesterone regulates catechol-O-methyl transferase gene expression in breast cancer cells: Distinct effect of progesterone receptor isoforms

Medical Management of Uterine Fibroids

Contact Info

Product

Resources

About