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Steven S Witkin - One of the best experts on this subject based on the ideXlab platform.
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Catechol-O-Methyltransferase gene polymorphism and vulvar pain in women with vulvodynia.
American journal of obstetrics and gynecology, 2016Co-Authors: Insiyyah Y Patanwala, Georgine Lamvu, William J Ledger, Kathryn Witzeman, Richard Marvel, Andrea Rapkin, Ann Marie Bongiovanni, Jessica Feranec, Steven S WitkinAbstract:The underlying causes of vulvar pain in women with vulvodynia remain poorly understood. Catechol-O-Methyltransferase, an enzyme that metabolizes Catecholamines, is a neuromodulator that is involved with perception and sensitivity to pain. The Catechol-O-Methyltransferase gene is polymorphic, and a single nucleotide polymorphism is associated with low activity and heightened pain sensitivity. The variant allele that encodes this polymorphism commonly is called the "L allele" because of its low enzyme activity as opposed to the normal H (high activity) allele. The methionine-containing Catechol-O-Methyltransferase protein coded by the L allele results in elevated Catecholamine levels, reduced inactivation of the dopaminergic and adrenergic systems, and increased sensitivity to pain. This polymorphism not only may decrease the pain threshold in response to acute pain but also may facilitate the development of chronic pain. Therefore, the objective of our study was to assess whether a variation in the Catechol-O-Methyltransferase genotype is involved in increased pain sensitivity in women with vulvodynia. We conducted a prospective cohort study. Buccal swabs were collected from 167 white women with vulvodynia and 107 control subjects; the DNA was tested for a single nucleotide polymorphism at position 158 (rs4680) in the Catechol-O-Methyltransferase gene. Women with vulvodynia had a marginally increased, yet not significant, prevalence of the Catechol-O-Methyltransferase genotype that is associated with high activity of the coded protein: 32.9% in the women with vulvodynia, as opposed to 21.5% in the control subjects (odds ratio, 1.80; 95% confidence interval, 1.02-3.15). Subgrouping the cases based on pain frequency revealed that the elevated occurrence of this Catechol-O-Methyltransferase genotype was present in 40.6% of the subset of women who experienced pain only with sexual intercourse vs only 21.5% of control subjects (odds ratio, 2.50; 95% confidence interval, 1.27-4.93). Also, women with primary vulvodynia had a significantly higher prevalence of the H allele than did the control subjects (62.9% vs 48.1%; odds ratio, 1.82; 95% confidence interval, 1.05-3.17). Increased pain sensitivity in women with vulvodynia is not due to a genetically determined low Catechol-O-Methyltransferase enzyme activity. Other mechanisms may account for alterations in Catechol-O-Methyltransferase activity in women with pain that is limited to intercourse or primary vulvodynia that contributes to pain sensitivity. Copyright © 2016 Elsevier Inc. All rights reserved.
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Catechol-O-Methyltransferase gene polymorphism and vulvar pain in women with vulvodynia.
American Journal of Obstetrics and Gynecology, 2016Co-Authors: Insiyyah Y Patanwala, Georgine Lamvu, William J Ledger, Kathryn Witzeman, Richard Marvel, Andrea Rapkin, Ann Marie Bongiovanni, Jessica Feranec, Steven S WitkinAbstract:Background The underlying causes of vulvar pain in women with vulvodynia remain poorly understood. Catechol- O -methyltransferase, an enzyme that metabolizes Catecholamines, is a neuromodulator that is involved with perception and sensitivity to pain. The Catechol- O -methyltransferase gene is polymorphic, and a single nucleotide polymorphism is associated with low activity and heightened pain sensitivity. The variant allele that encodes this polymorphism commonly is called the "L allele" because of its low enzyme activity as opposed to the normal H (high activity) allele. Objective The methionine-containing Catechol- O -methyltransferase protein coded by the L allele results in elevated Catecholamine levels, reduced inactivation of the dopaminergic and adrenergic systems, and increased sensitivity to pain. This polymorphism not only may decrease the pain threshold in response to acute pain but also may facilitate the development of chronic pain. Therefore, the objective of our study was to assess whether a variation in the Catechol- O -methyltransferase genotype is involved in increased pain sensitivity in women with vulvodynia. Study Design We conducted a prospective cohort study. Methods Buccal swabs were collected from 167 white women with vulvodynia and 107 control subjects; the DNA was tested for a single nucleotide polymorphism at position 158 (rs4680) in the Catechol- O -methyltransferase gene. Results Women with vulvodynia had a marginally increased, yet not significant, prevalence of the Catechol- O -methyltransferase genotype that is associated with high activity of the coded protein: 32.9% in the women with vulvodynia, as opposed to 21.5% in the control subjects (odds ratio, 1.80; 95% confidence interval, 1.02–3.15). Subgrouping the cases based on pain frequency revealed that the elevated occurrence of this Catechol- O -methyltransferase genotype was present in 40.6% of the subset of women who experienced pain only with sexual intercourse vs only 21.5% of control subjects (odds ratio, 2.50; 95% confidence interval, 1.27–4.93). Also, women with primary vulvodynia had a significantly higher prevalence of the H allele than did the control subjects (62.9% vs 48.1%; odds ratio, 1.82; 95% confidence interval, 1.05–3.17). Conclusion Increased pain sensitivity in women with vulvodynia is not due to a genetically determined low Catechol- O -methyltransferase enzyme activity. Other mechanisms may account for alterations in Catechol- O -methyltransferase activity in women with pain that is limited to intercourse or primary vulvodynia that contributes to pain sensitivity.
Richard M. Weinshilboum - One of the best experts on this subject based on the ideXlab platform.
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Catechol O-Methyltransferase pharmacogenomics and selective serotonin reuptake inhibitor response
Pharmacogenomics Journal, 2010Co-Authors: Yuan Ji, Joanna M. Biernacka, Karen Snyder, Maureen S. Drews, Linda L. Pelleymounter, Colin L. Colby, Liewei M Wang, David A. Mrazek, Richard M. WeinshilboumAbstract:Catechol O- methyltransferase pharmacogenomics and selective serotonin reuptake inhibitor response
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Human liver Catechol‐O‐methyltransferase pharmacogenetics
Clinical Pharmacology & Therapeutics, 1990Co-Authors: Blanka Boudíková, Carol L. Szumlanski, Bonnie L. Maidak, Richard M. WeinshilboumAbstract:Catechol-O-Methyltransferase activity and thermal stability in the human red blood cell are controlled by a common genetic polymorphism. Approximately 25% to 30% of a randomly selected population sample is homozygous for the traits of low Catechol-O-Methyltransferase activity and thermolabile enzyme in the red blood cell. We tested the hypothesis that the Catechol-O-Methyltransferase genetic polymorphism might also control those same characteristics of the enzyme in an important human drug-metabolizing organ, the liver. Catechol-O-Methyltransferase enzyme activity and thermal stability were measured in 99 hepatic biopsy samples obtained during clinically indicated surgery. The frequency distribution of heated/control ratios, a measure of enzyme thermal stability, was bimodal, with 28% of samples included in a subgroup with thermolabile enzyme. There were no sex-related differences in hepatic Catechol-O-Methyltransferase thermal stability. However, Catechol-O-Methyltransferase enzyme activity in hepatic tissue from male subjects was significantly higher than that in samples from female subjects: 61.3 ± 20.2 units/mg protein (mean ± SD; n = 50) versus 46.6 ± 22.2 units/mg protein (n = 49; p = 0.0002). There was a significant correlation of hepatic Catechol-O-Methyltransferase activity and thermal stability in samples from both female (rs = 0.698; p = 0.0001) and male subjects (rs = 0.429; p = 0.002). Finally, when both red blood cell Catechol-O-Methyltransferase activity and thermal stability were measured in blood samples from 34 of these patients, there was a significant correlation between Catechol-O-Methyltransferase heated/control ratios and levels of enzyme activity in hepatic tissue and in red blood cell lysates. These findings indicate that the genetic polymorphism that controls Catechol-O-Methyltransferase activity level and thermal stability in red blood cells also controls those same properties of the enzyme in the human liver. Clinical Pharmacology and Therapeutics (1990) 48, 381–389; doi:10.1038/clpt.1990.166
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Human liver Catechol-O-Methyltransferase pharmacogenetics.
Clinical pharmacology and therapeutics, 1990Co-Authors: Blanka Boudíková, Carol L. Szumlanski, Bonnie L. Maidak, Richard M. WeinshilboumAbstract:Catechol-O-Methyltransferase activity and thermal stability in the human red blood cell are controlled by a common genetic polymorphism. Approximately 25% to 30% of a randomly selected population sample is homozygous for the traits of low Catechol-O-Methyltransferase activity and thermolabile enzyme in the red blood cell. We tested the hypothesis that the Catechol-O-Methyltransferase genetic polymorphism might also control those same characteristics of the enzyme in an important human drug-metabolizing organ, the liver. Catechol-O-Methyltransferase enzyme activity and thermal stability were measured in 99 hepatic biopsy samples obtained during clinically indicated surgery. The frequency distribution of heated/control ratios, a measure of enzyme thermal stability, was bimodal, with 28% of samples included in a subgroup with thermolabile enzyme. There were no sex-related differences in hepatic Catechol-O-Methyltransferase thermal stability. However, Catechol-O-Methyltransferase enzyme activity in hepatic tissue from male subjects was significantly higher than that in samples from female subjects: 61.3 ± 20.2 units/mg protein (mean ± SD; n = 50) versus 46.6 ± 22.2 units/mg protein (n = 49; p = 0.0002). There was a significant correlation of hepatic Catechol-O-Methyltransferase activity and thermal stability in samples from both female (rs = 0.698; p = 0.0001) and male subjects (rs = 0.429; p = 0.002). Finally, when both red blood cell Catechol-O-Methyltransferase activity and thermal stability were measured in blood samples from 34 of these patients, there was a significant correlation between Catechol-O-Methyltransferase heated/control ratios and levels of enzyme activity in hepatic tissue and in red blood cell lysates. These findings indicate that the genetic polymorphism that controls Catechol-O-Methyltransferase activity level and thermal stability in red blood cells also controls those same properties of the enzyme in the human liver. Clinical Pharmacology and Therapeutics (1990) 48, 381–389; doi:10.1038/clpt.1990.166
Insiyyah Y Patanwala - One of the best experts on this subject based on the ideXlab platform.
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Catechol-O-Methyltransferase gene polymorphism and vulvar pain in women with vulvodynia.
American journal of obstetrics and gynecology, 2016Co-Authors: Insiyyah Y Patanwala, Georgine Lamvu, William J Ledger, Kathryn Witzeman, Richard Marvel, Andrea Rapkin, Ann Marie Bongiovanni, Jessica Feranec, Steven S WitkinAbstract:The underlying causes of vulvar pain in women with vulvodynia remain poorly understood. Catechol-O-Methyltransferase, an enzyme that metabolizes Catecholamines, is a neuromodulator that is involved with perception and sensitivity to pain. The Catechol-O-Methyltransferase gene is polymorphic, and a single nucleotide polymorphism is associated with low activity and heightened pain sensitivity. The variant allele that encodes this polymorphism commonly is called the "L allele" because of its low enzyme activity as opposed to the normal H (high activity) allele. The methionine-containing Catechol-O-Methyltransferase protein coded by the L allele results in elevated Catecholamine levels, reduced inactivation of the dopaminergic and adrenergic systems, and increased sensitivity to pain. This polymorphism not only may decrease the pain threshold in response to acute pain but also may facilitate the development of chronic pain. Therefore, the objective of our study was to assess whether a variation in the Catechol-O-Methyltransferase genotype is involved in increased pain sensitivity in women with vulvodynia. We conducted a prospective cohort study. Buccal swabs were collected from 167 white women with vulvodynia and 107 control subjects; the DNA was tested for a single nucleotide polymorphism at position 158 (rs4680) in the Catechol-O-Methyltransferase gene. Women with vulvodynia had a marginally increased, yet not significant, prevalence of the Catechol-O-Methyltransferase genotype that is associated with high activity of the coded protein: 32.9% in the women with vulvodynia, as opposed to 21.5% in the control subjects (odds ratio, 1.80; 95% confidence interval, 1.02-3.15). Subgrouping the cases based on pain frequency revealed that the elevated occurrence of this Catechol-O-Methyltransferase genotype was present in 40.6% of the subset of women who experienced pain only with sexual intercourse vs only 21.5% of control subjects (odds ratio, 2.50; 95% confidence interval, 1.27-4.93). Also, women with primary vulvodynia had a significantly higher prevalence of the H allele than did the control subjects (62.9% vs 48.1%; odds ratio, 1.82; 95% confidence interval, 1.05-3.17). Increased pain sensitivity in women with vulvodynia is not due to a genetically determined low Catechol-O-Methyltransferase enzyme activity. Other mechanisms may account for alterations in Catechol-O-Methyltransferase activity in women with pain that is limited to intercourse or primary vulvodynia that contributes to pain sensitivity. Copyright © 2016 Elsevier Inc. All rights reserved.
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Catechol-O-Methyltransferase gene polymorphism and vulvar pain in women with vulvodynia.
American Journal of Obstetrics and Gynecology, 2016Co-Authors: Insiyyah Y Patanwala, Georgine Lamvu, William J Ledger, Kathryn Witzeman, Richard Marvel, Andrea Rapkin, Ann Marie Bongiovanni, Jessica Feranec, Steven S WitkinAbstract:Background The underlying causes of vulvar pain in women with vulvodynia remain poorly understood. Catechol- O -methyltransferase, an enzyme that metabolizes Catecholamines, is a neuromodulator that is involved with perception and sensitivity to pain. The Catechol- O -methyltransferase gene is polymorphic, and a single nucleotide polymorphism is associated with low activity and heightened pain sensitivity. The variant allele that encodes this polymorphism commonly is called the "L allele" because of its low enzyme activity as opposed to the normal H (high activity) allele. Objective The methionine-containing Catechol- O -methyltransferase protein coded by the L allele results in elevated Catecholamine levels, reduced inactivation of the dopaminergic and adrenergic systems, and increased sensitivity to pain. This polymorphism not only may decrease the pain threshold in response to acute pain but also may facilitate the development of chronic pain. Therefore, the objective of our study was to assess whether a variation in the Catechol- O -methyltransferase genotype is involved in increased pain sensitivity in women with vulvodynia. Study Design We conducted a prospective cohort study. Methods Buccal swabs were collected from 167 white women with vulvodynia and 107 control subjects; the DNA was tested for a single nucleotide polymorphism at position 158 (rs4680) in the Catechol- O -methyltransferase gene. Results Women with vulvodynia had a marginally increased, yet not significant, prevalence of the Catechol- O -methyltransferase genotype that is associated with high activity of the coded protein: 32.9% in the women with vulvodynia, as opposed to 21.5% in the control subjects (odds ratio, 1.80; 95% confidence interval, 1.02–3.15). Subgrouping the cases based on pain frequency revealed that the elevated occurrence of this Catechol- O -methyltransferase genotype was present in 40.6% of the subset of women who experienced pain only with sexual intercourse vs only 21.5% of control subjects (odds ratio, 2.50; 95% confidence interval, 1.27–4.93). Also, women with primary vulvodynia had a significantly higher prevalence of the H allele than did the control subjects (62.9% vs 48.1%; odds ratio, 1.82; 95% confidence interval, 1.05–3.17). Conclusion Increased pain sensitivity in women with vulvodynia is not due to a genetically determined low Catechol- O -methyltransferase enzyme activity. Other mechanisms may account for alterations in Catechol- O -methyltransferase activity in women with pain that is limited to intercourse or primary vulvodynia that contributes to pain sensitivity.
Pekka T. Männistö - One of the best experts on this subject based on the ideXlab platform.
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No change of brain extracellular Catecholamine levels after acute Catechol-O-Methyltransferase inhibition: a microdialysis study in anaesthetized rats
European Journal of Pharmacology, 1998Co-Authors: Thomas Wirth, Marko Huotari, Kirsti Laitinen, Ewen Macdonald, Pekka T. MännistöAbstract:Catechol-O-Methyltransferase inhibitors have been newly introduced as adjunct drugs to the levodopa/dopa decarboxylase inhibitor therapy in Parkinson's disease. When given alone, Catechol-O-Methyltransferase inhibitors seem to affect behaviour. We wanted to determine whether the concentrations of free amine would be increased by Catechol-O-Methyltransferase inhibition with tolcapone and underpin the positive behavioural effects. To this end, dopamine and noradrenaline levels were analyzed in the microdialysis perfusion fluid collected from several brain regions in chloral hydrate anaesthetized rats. We also analyzed the turnover rate of Catecholamines in the brain after single doses of tolcapone and entacapone using the α-methyl-p-tyrosine method. On their own, tolcapone (at 10 or 30 mg/kg) did not elevate dopamine or noradrenaline levels in any brain region studied although the formation of Catechol-O-Methyltransferase-dependent metabolites was strongly reduced. Neither tolcapone nor entacapone (at 30 mg/kg) affected the turnover rate of Catecholamines. It seems that Catechol-O-Methyltransferase inhibitors do not alter behaviour by elevating extracellular levels of free Catecholamines levels but other explanations are needed.
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Beneficial effects of co-administration of Catechol-O-Methyltransferase inhibitors and L-dihydroxyphenylalanine in rat models of depression.
European journal of pharmacology, 1995Co-Authors: Pekka T. Männistö, Pekka Rauhala, Aavo Lang, Eero VasarAbstract:Abstract The administration of Catechol- O -methyltransferase inhibitors alone changed neither the behavior of the rats in two animal models of depression, the forced swimming test (entacapone and tolcapone) or in the learned helplessness paradigm (tolcapone), nor the locomotor activity. l -Dihydroxyphenylalanine (L-DOPA) and carbidopa treatment as such decreased motility but did not improve the behavior in the antidepressant tests. Co-administration of Catechol- O -methyltransferase inhibitors and L-DOPA/carbidopa increased the performance of rats in both tests without increasing locomotor activity. Catechol- O -methyltransferase inhibitors could be beneficial as adjunct drugs of L-DOPA not only in Parkinson's disease but also in the coincident depressive illness.
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Modulation of rat brain endogenous dopamine metabolism by new inhibitors of Catechol O-Methyltransferase.
European journal of pharmacology, 1993Co-Authors: M. Törnwall, Päivi Tuomainen, Pekka T. MännistöAbstract:The extraneuronal and intraneuronal metabolism of rat brain endogenous dopamine was stimulated by amphetamine (5 mg/kg) and pimozide (2 mg/kg), respectively. Additional metabolic effects of two inhibitors of Catechol O-Methyltransferase (entacapone and tolcapone (both 30 mg/kg)) and a putative central uptake2 inhibitor (CGP 28014 (30 mg/kg)) were assessed. Amphetamine increased striatal dopamine and 3-methoxytyramine and decreased 3,4-dihydroxyphenylacetic acid (DOPAC) levels. The latter two effects were reversed by tolcapone and CGP 28014, but not by entacapone. Tolcapone, CGP 28014 and even entacapone decreased striatal homovanillic acid (HVA) levels. Pimozide-induced striatal DOPAC levels were further increased by tolcapone and CGP 28014. Both substances also decreased striatal HVA levels. Striatal 3-methoxytyramine levels were significantly lowered only by tolcapone. Our results show that enhanced central dopamine metabolism is modified by the inhibition of Catechol O-Methyltransferase even in the absence of L-3,4-dihydroxyphenylalanine (L-DOPA). The results also suggest that the mechanism of action of CGP 28014 may be other than true inhibition of Catechol O-Methyltransferase.
Ayman Al-hendy - One of the best experts on this subject based on the ideXlab platform.
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Elevated expression of Catechol-O-Methyltransferase is associated with labor and increased prostaglandin E2 production by human fetal membranes
American Journal of Obstetrics and Gynecology, 2009Co-Authors: Hassan Harirah, Melissa J. Wentz, Chandrasekhar Thota, Wahiduz A. Zaman, Ayman Al-hendyAbstract:Objective The purpose of this study was to evaluate the expression and function of Catechol-O-Methyltransferase in human fetal membranes at term. Study Design Fetal membranes obtained from women between 38-42 weeks of gestation, after (1) vaginal delivery with spontaneous labor and (2) prelabor elective cesarean section (no labor), were assayed for Catechol-O-Methyltransferase expression using quantitative real-time polymerase chain reaction analysis, immunohistochemistry, and Western blot analysis. Prostaglandin E2 secretion from amnion and choriodecidua explants treated with or without Catechol-O-Methyltransferase inhibitor was assayed by enzyme-linked immunosorbent analysis. Results Amnion layer of fetal membranes from laboring women expressed significantly higher levels of Catechol-O-Methyltransferase, compared with those from women with no labor. Catechol-O-Methyltransferase was higher in the amnion layer than in choriodecidua. Selective Catechol-O-Methyltransferase inhibition significantly decreased prostaglandin E2 production from fetal membranes. Conclusion Labor increases Catechol-O-Methyltransferase expression in the amnion of human fetal membranes. Selective Catechol-O-Methyltransferase inhibition decreased prostaglandin E2 secretion in fetal explant cultures, suggesting a role for Catechol-O-Methyltransferase in human labor and delivery.
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Elevated expression of Catechol-O-Methyltransferase is associated with labor and increased prostaglandin E(2) production by human fetal membranes.
American journal of obstetrics and gynecology, 2009Co-Authors: Hassan Harirah, Melissa J. Wentz, Chandrasekhar Thota, Wahiduz Zaman, Ayman Al-hendyAbstract:The purpose of this study was to evaluate the expression and function of Catechol-O-Methyltransferase in human fetal membranes at term. Fetal membranes obtained from women between 38-42 weeks of gestation, after (1) vaginal delivery with spontaneous labor and (2) prelabor elective cesarean section (no labor), were assayed for Catechol-O-Methyltransferase expression using quantitative real-time polymerase chain reaction analysis, immunohistochemistry, and Western blot analysis. Prostaglandin E(2) secretion from amnion and choriodecidua explants treated with or without Catechol-O-Methyltransferase inhibitor was assayed by enzyme-linked immunosorbent analysis. Amnion layer of fetal membranes from laboring women expressed significantly higher levels of Catechol-O-Methyltransferase, compared with those from women with no labor. Catechol-O-Methyltransferase was higher in the amnion layer than in choriodecidua. Selective Catechol-O-Methyltransferase inhibition significantly decreased prostaglandin E(2) production from fetal membranes. Labor increases Catechol-O-Methyltransferase expression in the amnion of human fetal membranes. Selective Catechol-O-Methyltransferase inhibition decreased prostaglandin E(2) secretion in fetal explant cultures, suggesting a role for Catechol-O-Methyltransferase in human labor and delivery.
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Regulation of Catechol-O-Methyltransferase Expression in Human Myometrial Cells
Obstetrics & Gynecology, 2006Co-Authors: Melissa J. Wentz, Mohammad Jamaluddin, Robert E. Garfield, Ayman Al-hendyAbstract:Catechol-O-Methyltransferase catalyzes the transfer of a methyl group from S-adenosyl-methio-nine to one of the phenolic hydroxyl groups in a variety of Catechols including Catechol estrogens and Catecholamine neurotransmitters.1,2 During estrogen metabolism, Catechol-O-Methyltransferase converts the Catechol estrogens, 2- or 4-hydroxyestrogen, to 2-or 4-methoxyestrogen. These estrogen metabolites have been shown to modulate the local effects of estrogen.3–9 Because Catechol-O-Methyltransferase activity ultimately controls levels of these metabolites, it appears to be a key factor in regulating the cellular estrogenic milieu. Catechol-O-Methyltransferase is present in many types of tissues, including those involved in reproduction (Salih SM, Salama SA, Jamaluddin M, Nagamani M, Al-Hendy A. Cyclic Variations of Catechol-omethyltransferase [COMT] expression in human endometrium and hormonal regulation of COMT in human stromal endometrial cell line [abstract]. J Soc Gynecol Investig 2006;13:265A).5,10–12 Distinct variations in Catechol-O-Methyltransferase expression were detected in endometrium samples taken from cycling women, in which Catechol-O-Methyltransferase expression levels were higher in proliferative endometrium compared with secretory endometrium (Salih et al).13 Changes in Catechol-O-Methyltransferase activity in reproductive tissues were also detected during pregnancy. Catechol-O-methyltrans ferase activity was higher in decidua vera tissues taken from term pregnant women than in tissues taken from women in early pregnancy.12 Placental tissues taken from pregnant women at term also contained high levels of Catechol-O-Methyltransferase activity.10,11 Hormones were shown to influence Catechol-O-Methyltransferase expression in a tissue-specific manner.13–16 Results from computer-based bioinformatic analysis of the Catechol-O-Methyltransferase promoter revealed the presence of multiple half-sites of the estrogen-response element, a half-site for the glucocorticoid-response element, and multiple sites for nuclear factor κB. In this study, we examined the regulation of Catechol-O-Methyltransferase expression in human myometrial cells. Catechol-O-Methyltransferase expression was assessed by reverse transcription–polymerase chain reaction or Western blot analyses in primary human myometrium cells after treatment with progesterone, estrogen, or tumor necrosis factor α (TNFα), a cytokine associated with parturition. Luciferase assays were conducted using immortalized human myometrial cells containing a lucif-erase reporter controlled by the Catechol-O-Methyltransferase promoter, which were treated with estrogen or progesterone to confirm results obtained from reverse transcription–polymerase chain reaction and Western blot analyses. In addition, immortalized human myome-trial cells containing an estrogen response element–lucif-erase reporter gene were treated with estrogen and 2-hydroxyestrogen to measure the impact of this metabolite on estrogen-mediated transactivation.