Free radical generation by redox cycling of estrogens

Liehr, Joachim G.; Roy, Deodutta

doi:10.1016/0891-5849(90)90108-u

Cited by 287 publications

(198 citation statements)

References 41 publications

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“…A possible explanation for the sexually dimorphic COMT gene effect could rely on the well investigated modulatory role of COMT on tissue levels of catecholestrogens (Liehr and Roy, 1990;Liehr and Ricci, 1996) since COMT is the principal enzyme in the conjugation pathway for estrogens. Accordingly, it has been shown that serum estrogen levels in women are significantly associated with the COMT genotype with Val/Val women displaying the lowest estrogen concentrations (Worda et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

Gender-Dependent Association of the Functional Catechol-O-Methyltransferase Val158Met Genotype with Sensation Seeking Personality Trait

Lang

Bajbouj

Sander

et al. 2007

Neuropsychopharmacol

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The gene encoding cathechol-O-methyltransferase (COMT) contains a common functional missense polymorphism (Val158Met) that regulates dopamine in an allele-dependent manner. A pivotal role of dopamine neurotransmission in the prefrontal cortex has been implicated in drug-seeking behavior and related personality traits, such as sensation seeking, with some evidence for a gender-specific association. Here, we tested the hypothesis that the COMT Val158Met polymorphism modulates the personality dimension, sensation seeking, in a gender-dependent manner. Study sample included 214 male (age 38.1712.6 years) and 218 female (age 36.1713.6 years) healthy volunteers, who were assessed with Zuckerman's sensation-seeking scale and genotyped for the Val158Met polymorphism (dbSNP:rs4680). Univariate analysis of variance showed that the sensation seeking score was significantly affected by a COMT genotype Â gender interaction (F ¼ 5.330, df ¼ 2, p ¼ 0.005). The Val158Met polymorphism was associated with the sensation seeking personality trait in women only. The highest scores in the sensation-seeking scale and in three of the four subscales were observed in female subjects with the Val/Val genotype relative to women carrying the Met allele. Our results suggest that high COMT enzyme activity associated with the Val allele predisposes to high sensation seeking scores in female subjects and add to increasing evidence for a gender specific role of COMT in normal and dysfunctional behavior.

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Section: Discussionmentioning

confidence: 99%

Gender-Dependent Association of the Functional Catechol-O-Methyltransferase Val158Met Genotype with Sensation Seeking Personality Trait

Lang

Bajbouj

Sander

et al. 2007

Neuropsychopharmacol

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“…The origin of this excess H 2 O 2 in tissue is principally O 2 •− (see Fig. 1) and involves the enzyme superoxide dismutase (SOD) [4,6,12]. The prooxidant effect of 3,4-E1Q was especially profound in the uterus homogenate of ovariectomized animals.…”

Section: Discussionmentioning

confidence: 99%

“…From these ortho-quinones, superoxide radical anion (O 2 •− ) is generated from molecular oxygen via semiquinone formation in a perpetual cyclic mechanism known as redox cycling, as exemplified in Fig. 1 [4]. Therefore, this redox cycling induces oxidative stress that has been linked to estrogen-related carcinogenicity [5,6].…”

Section: Introductionmentioning

confidence: 99%

Comparison of estrogen-derived ortho-quinone and para-quinol concerning induction of oxidative stress

Rivera-Portalatin

Vera-Serrano

Prókai-Tátrai

et al. 2007

The Journal of Steroid Biochemistry and Molecular Biology

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Ortho-quinones formed from catechol estrogens are considered prooxidants due to the production of superoxide radical anions through redox cycling via semiquinones. Para-quinols have been identified as novel metabolites of and as the major products of hydroxyl-radical scavenging by estrogens. Cycling of these compounds has also been discovered, because they are converted back to the parent estrogen via reductive aromatization in vitro and in vivo. We hypothesized that, unlike ortho-quinones, para-quinols do not induce oxidative stress due to this cycling. Like the estrogen itself, the 17β-estradiol-derived para-quinol (10β,17β-dihydroxyestra-1,4-diene-3-one) did not induce oxidative stress, as the rate of hydrogen peroxide production during the incubations of the compounds in various tissue homogenates was not significantly different from that of the control experiments performed without the addition of a test compound. We also confirmed that the estrogen metabolite estra-1,5(10)-dien-3,4,17-trione (estrone 3,4-quinone) was a profound prooxidant due to redox cycling, especially in uterine tissue. Therefore, we concluded that para-quinols do not induce oxidative stress.

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“…Furthermore, the COMT gene has an estrogenic response element in its promoter region, so certain haplotypes containing this could produce differential expression of COMT depending upon estrogen levels (64). As a key enzyme in the conjugation of catecholestrogens (65), COMT genotype also affects circulating levels of estrogen (66), suggesting a complex bidirectional interaction between estrogenic hormones and COMT haplotypes which could, presumably, impact psychiatric risk in a sex-specific manner.…”

Section: Discussionmentioning

confidence: 99%

Catechol-O-Methyltransferase Contributes to Genetic Susceptibility Shared Among Anxiety Spectrum Phenotypes

Hettema

Bukszár

et al. 2008

Biological Psychiatry

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Free radical generation by redox cycling of estrogens

Cited by 287 publications

References 41 publications

Gender-Dependent Association of the Functional Catechol-O-Methyltransferase Val158Met Genotype with Sensation Seeking Personality Trait

Gender-Dependent Association of the Functional Catechol-O-Methyltransferase Val158Met Genotype with Sensation Seeking Personality Trait

Comparison of estrogen-derived ortho-quinone and para-quinol concerning induction of oxidative stress

Catechol-O-Methyltransferase Contributes to Genetic Susceptibility Shared Among Anxiety Spectrum Phenotypes

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