Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Hydroxyestrones”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 253 records · Page 14Linked to original sources
PubMed1999

The Physical Activity for Total Health (PATH) Study: rationale and design.

PURPOSE: Physical activity has been associated with a decreased risk for breast cancer. Mechanisms for this association may involve hormonal pathways. The Physical Activity for Total Health study is testing the effect of a 1-yr moderate intensity physical activity intervention on the endogenous sex hormone profile of postmenopausal women in a randomized controlled study. METHODS: Women (N = 168) who are aged 55-75 yr, not using sex hormones, sedentary, nonsmokers, have no endocrine-related disease or cancer, and with body mass index of 25.0 or greater, are eligible. Women are recruited through mass mailings and media advertising and are randomized to either a 1-yr moderate intensity aerobic and strength training exercise program (monitored group exercise sessions plus home exercise) or a control program (stretching classes). RESULTS: Serum hormones to be assayed at baseline and at the end of the study include: total estrone, total estradiol, free estradiol, percent bioavailable estradiol, estrone sulfate, sex hormone binding globulin, albumin, testosterone, free testosterone, androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate, insulin, glucose, and triglycerides. Other outcome measures include: the ratio of urinary 2-hydroxyestrone: 16alpha-hydroxyestrone (an estrogen metabolite ratio that may be associated with risk for breast cancer), weight, body mass index, total fat mass, and body fat distribution (waist:hip circumference ratio, DEXA scan, and abdominal fat measured by computed tomography). CONCLUSION: This study is the first to examine the effect of change in physical activity level on sex hormones in postmenopausal women. It will provide insight into possible mechanisms through which physical activity might be associated with reduced risk of breast cancer.

Aged↗
PubMed2002

Biotransformation and bioconcentration of steroid estrogens by Chlorella vulgaris.

The biotransformation and bioconcentration of natural and synthetic steroid estrogens by Chlorella vulgaris were investigated by using batch-shaking experiments with incubation for 48 h in the light or dark. Estradiol and estrone were interconvertible in both light and dark conditions; however, this biotransformation showed a preference for estrone. In the light, 50% estradiol was further metabolized to an unknown product. Apart from biotransformation, estrone, as well as hydroxyestrone, estriol, and ethinylestradiol, was relatively stable in the algal culture, whereas estradiol valerate was hydrolyzed to estradiol and then to estrone within 3 h of incubation. All of the tested estrogens exhibited a degree of partitioning to C. vulgaris; however, the concentrations of estriol, hydroxyestrone, ethinylestradiol, and estradiol valerate were always below the quantification limits. For estradiol and estrone, the partitioning of these estrogens in the algal extracts to the filtrates was <6% of the total amount present. The average concentration factor for estrone was ca. 27; however, the concentration factor for estradiol was not reported since no equilibrium was reached between the aqueous solution and that within the cells due to continuing biotransformation.

Chlorella↗
PubMed1977

Evidence for 16beta-hydroxylation of estrogens by guinea pig liver slices.

In an earlier communication, we conclusively proved that estrone-3-sulfate could be hydroxylated in the 16alpha position by guinea pig liver slices. Disulfates of 16alpha-hydroxyestrone and estriol were identified. Suggestive evidence for 6-hydroxylated metabolites was also mentioned. A careful reinvestigation has now shown that the steroid disulfate fraction is composed of 16alpha- and 16beta-hydroxylated steroids. 16beta-Hydroxyestrone in particular is an important quantitative metabolite of estradiol-17 beta. It is concluded that no firm evidence is available for the formation of 6-hydroxysteroids in the tissue system under consideration.

Animals↗
PubMed1998

Interactions between hormones and chemicals in breast cancer.

Development of breast cancer in women is dependent on diverse factors, including genetic predisposition, exposure to both exogenous and endogenous chemicals, which can modulate initiation, promotion and progression of this disease, and the timing of exposure to these agents. Several compounds--including 16 alpha-hydroxyestrone (16 alpha-OHE1), catecholestrogens, and aromatic amines--have been proposed as initiators of mammary carcinogenesis in humans; however, their role as genotoxins is unconfirmed. Lifetime exposure to estrogens has been established as an important risk factor for breast cancer, and it has been suggested that xenoestrogens may directly add to the hormonal risk or indirectly increase risk by decreasing 2-hydroxyestrone (2-OHE1)/16 alpha-OHE1 metabolite ratios. Results of recent studies suggest that chemical-induced modulation of 2-OHE1/16 alpha-OHE1 metabolite ratios is not predictive of xenoestrogens or mammary carcinogens. Moreover, based on current known dietary intakes of natural and xenoestrogenic/antiestrogenic chemicals, it is unlikely that xenoestrogens contribute significantly to a woman's overall lifetime exposure to estrogens. More information is required on the identities and serum levels of both natural and xenoendocrine active compounds, their concentrations in serum, and the mammary gland and levels of these compounds at critical periods of exposure.

Animals↗
PubMed1999

Effects of soy intake on sex hormone metabolism in premenopausal women.

Studies suggest that phytoestrogens in soy products may impart hormonal effects that protect women against breast cancer. Limited research suggests that intake of soy products high in isoflavonoid phytoestrogens affects sex hormone metabolism, but it is unknown whether phytoestrogens in soy have any effect on menstrual function or serum sex hormones in women on common hormone therapies, such as oral contraceptives (OC). We studied the effects of soy in 36 premenopausal women, 20 of whom used OC. Subjects consumed their normal diet for two menstrual cycles and added a soy beverage containing 20 g of protein and 38 mg of total isoflavones to their usual diet for another two menstrual cycles. No significant differences were observed in serum estrone, estradiol, sex hormone-binding globulin, dehydroepiandrosterone sulfate, prolactin, or progesterone concentrations with soy feeding in the non-OC or the OC group. No changes in menstrual cycle length or the urinary estrogen metabolite ratio of 2-hydroxyestrone to 16 alpha-hydroxyestrone were seen with soy feeding in the non-OC or the OC group. Levels of urinary estrogen metabolites were significantly different between the non-OC and the OC group. Thus soy consumption had no significant effect on the menstrual cycle, serum sex hormones, or urinary estrogen metabolite ratio in premenopausal OC or non-OC users.

Adolescent↗
PubMed1975

The affinity of catechol estrogens for estrogen receptors in the pituitary and anterior hypothalamus of the rat.

The purpose of these experiments was to evaluate the potential for interaction between 2-hydroxyestrone and 2-hydroxyestradiol and estrogen receptors in rat pituitary and anterior hypothalamus. The 150,000 X g supernatant fractions of these tissues were prepared, the estrogen receptor-site concentration was measured, and the relative abilities of unlabelled estradiol, estrone, 2-hydroxyestradiol and 2-hydroxyestrone to compete with [3H]estradiol for estrogen binding sites was determined. From these results, and the previously determined association constant for [3H]estradiol, 10(10)M-1, the association constants of the other estrogens were calculated. The introduction of the 2-hydroxy group caused only a modest reduction in the affinity of these estrogens for the receptors. The association constants of the 2-hydroxy derivatives were within one order of magnitude of those of the parent compounds. These results demonstrate the potential for interaction between catechol estrogens and estrogen receptor in rat brain and pituitary of a magnitude which could be biologically significant.

Animals↗
PubMed2005

Estrogen metabolites and systolic blood pressure in a population-based sample of postmenopausal women.

CONTEXT: Lower systolic blood pressure (SBP) and lower rates of coronary heart disease among premenopausal women compared with similarly aged men and postmenopausal women suggest that female sex hormones may confer cardiovascular protection. 2-Hydroxyestradiol, a product of 17beta-estradiol oxidative metabolism, inhibits the proliferation of vascular smooth muscle cells in vitro. The other major product of 17beta-estradiol oxidative metabolism, 16alpha-hydroxyestradiol, does not demonstrate similar inhibitory effects. Concentrations of 2-hydroxyestrone (2-OHE) and 16alpha-hydroxyestrone (16-OHE) in urine reflect the relative activity of the 2- and 16alpha-hydroxylation pathways of 17beta-estradiol. OBJECTIVE: The objective of this study was to determine the relationship between SBP and the ratio of 2-OHE to 16-OHE in urine. DESIGN AND PARTICIPANTS: This was a cross-sectional study of 80 postmenopausal women living in Cook County, Illinois. SETTING: This study was performed in an academic clinical laboratory. MAIN OUTCOME MEASURE: The main outcome measure was SBP. RESULTS: Women taking hormone replacement therapy had higher levels of urinary 2-OHE and 16-OHE, but their mean 2:16-OHE ratio and SBP did not differ from that of women not taking hormone replacement therapy. In a multivariate regression model that controlled for age, body mass index, race/ethnicity, and antihypertensive medication use, a sd increase in the 2:16-OHE ratio was associated with a 6.7-mm Hg decrease (P < 0.05) in SBP. CONCLUSIONS: The ratio of urinary 2-OHE to 16-OHE is a significant predictor of SBP among postmenopausal women and may reflect the effects of 2-hydroxyestradiol, a potent inhibitor of vascular smooth muscle cell proliferation.

Biomarkers↗
PubMed1997

Is there an association between exposure to environmental estrogens and breast cancer?

It was initially reported that levels of polychlorinated biphenyls (PCBs) or p,p'-DDE were elevated in breast cancer patients (serum or tissue) versus controls. These results, coupled with reports that selected environmental estrogens decreased 17beta-estradiol (E2) 2-hydroxylase activity and increased the ratio of 16alpha-hydroxyestrone/2-hydroxyestrone metabolites in MCF-7 human breast cancer cells, have led to the hypothesis that xenoestrogens are a preventable cause of breast cancer. More recent studies and analysis of organochlorine levels in breast cancer patients versus controls show that these contaminants are not elevated in the latter group. Moreover, occupational exposure to relatively high levels of PCBs and DDT/DDE are not associated with an increased incidence of breast cancer. A reexamination of the radiometric E2 2-hydroxylase assay in MCF-7 cells with diverse estrogens, antiestrogens, and carcinogens showed that the mammary carcinogen benzo[a]pyrene induced this response and the antiestrogen ICI 164,384 decreased E2 2-hydroxylase activity. Thus, E2 2-hydroxylase activity and the 16alpha-hydroxyestrone/2-hydroxyestrone metabolite ratio in MCF-7 cells does not predict xenoestrogens or mammary carcinogens.

Breast Neoplasms↗
PubMed2000

The effect of flaxseed and wheat bran consumption on urinary estrogen metabolites in premenopausal women.

Estrogen is metabolized along two competing pathways to form the 2-hydroxylated and the 16alpha-hydroxylated metabolites. Based on proposed differences in biological activities, the ratio of these metabolites, 2-hydroxyestrogen:16alpha-hydroxyestrone (2:16alpha-OHE1), has been used as a biomarker for breast cancer risk. Women with an elevated 2:16alpha-OHE1 ratio are hypothesized to be at a decreased risk of breast cancer. Flaxseed, the most significant source of plant lignans, and wheat bran, an excellent source of dietary fiber, have both been shown to have chemoprotective benefits. Some of these benefits may be attributable to their influence on endogenous sex hormone production and metabolism. We examined the effect of flaxseed consumption alone and in combination with wheat bran on urinary estrogen metabolites in premenopausal women. Sixteen premenopausal women were studied for four feeding treatments lasting two menstrual cycles each in a randomized cross-over design. During the four feeding treatments, subjects consumed their usual diets supplemented with baked goods containing no flaxseed or wheat bran, 10 g of flaxseed, 28 g of wheat bran, or 10 g of flaxseed plus 28 g of wheat bran/day. Urinary excretion of 2-hydroxyestrogen and 16alpha-hydroxyestrone, as well as their ratio, 2:16alpha-OHE1, were measured by enzyme immunoassay. Flaxseed supplementation significantly increased the urinary 2:16alpha-OHE1 ratio (P = 0.034), but wheat bran had no effect. These results suggest that flaxseed may be chemoprotective in premenopausal women.

Adolescent↗
PubMed2001

Do urinary estrogen metabolites reflect the differences in breast cancer risk between Singapore Chinese and United States African-American and white women?

Breast cancer risk is substantially lower in Singapore than in women from the United STATES: Part of the risk discrepancy is probably explained by differences in the production of endogenous estrogens, but differences in the pathway by which estrogen is metabolized may also play a role. We undertook a study to determine whether the ratio of urinary 2-hydroxyestrone (2OHE(1)):16alpha-hydroxyestrone (16alpha-OHE(1)) was higher in Singapore Chinese than in a group of United States (predominantly African-American) women living in Los ANGELES: We also wanted to determine whether any difference in estrogen metabolite ratio between these two groups of women was greater than that in estrone (E(1)), estradiol (E(2)) and estriol (E(3)). The participants in this study were randomly selected healthy, non-estrogen using women participating in the Singapore Chinese Health Study (n = 67) or the Hawaii/Los Angeles Multiethnic Cohort Study (n = 58). After adjusting for age and age at menopause, mean urinary 2-OHE(1) was only 23% (P = 0.03) higher in Singapore Chinese than in United States women, and there were no statistically significant differences in 16alpha-OHE(1) levels or in the ratio of 2-OHE(1):16alpha-OHE(1) between the two groups. The adjusted mean 2-OHE(1):16alpha-OHE(1) ratio was 1.63 in Singapore Chinese and 1.48 in United States women (P = 0.41). In contrast, the adjusted mean values of E1, E2, and E3 were 162% (P < 0.0001), 152% (P < 0.0001), and 92% (P = 0.0009) higher, respectively, in United States women than in Singapore Chinese women. Our study suggests that urinary E1, E2, and E3 reflect the differences in breast cancer risk between Singapore Chinese and United States women to a stronger degree than the estrogen metabolites 2OHE(1) and 16alpha-OHE(1) or the ratio of 2OHE(1):16alpha-OHE(1.)

Aged↗
PubMed2004

Effects of a moderate intensity exercise intervention on estrogen metabolism in postmenopausal women.

Physical activity has been associated with reduced breast cancer risk, potentially via hormonal pathways, and high urinary excretion of 2-hydroxyestrone (2-OH E(1)) relative to 16alpha-hydroxyestrone (16alpha-OH E(1)) also has been associated with reduced breast cancer risk. Studies suggest that body composition and exercise can influence estrogen metabolism. We determined the effects of a 12-month moderate intensity aerobic exercise intervention on urinary 2-OH E(1), 16alpha-OH E(1), and their ratio in overweight and obese, previously sedentary, postmenopausal women, ages 50-75 years. Women were randomized to a 12-month exercise intervention (n = 87) or stretching control group (n = 86); 170 completed the study. Urinary 2- and 16alpha-OH E(1) were measured in spot urines collected at baseline, 3, and 12 months. Body composition was measured at baseline and 12 months. Differences between exercisers and controls for excretion of estrogen metabolites were determined using general estimating equations. Further analyses assessed change in estrogen metabolites and their ratio by subgroups of change in body composition. Overall, there were no significant effects of the exercise intervention on 2-OH E(1), 16alpha-OH E(1), or their ratio (P > 0.05). There appeared to be an effect of change in intra-abdominal fat and adherence to the exercise intervention on change in the estrogen metabolites or their ratio. However, this did not reflect a potentially desirable change in estrogen metabolites associated with the exercise intervention. Thus, this 12-month moderate intensity exercise intervention did not significantly alter urinary excretion of 2-OH E(1), 16alpha-OH E(1), or their ratio in this population of women.

Aged↗
PubMedDate not supplied

Clinical effects of a proprietary combination isoflavone nutritional supplement in menopausal women: a pilot trial.

BACKGROUND: As they reach menopause, a majority of women living in Westernized countries experience climacteric symptoms. Hormone replacement therapy (HRT) has been used to remediate these symptoms. Recent studies, however, have suggested that HRT may increase the risk of developing breast cancer and cardiovascular disease (CVD). Therefore, many women are looking for alternative treatment options. PURPOSE: This trial was a pilot study to assess the effect of a nutritional supplement containing isoflavones from kudzu and red clover, along with other targeted nutrients on menopausal symptoms and markers of breast cancer and CVD risk. Twenty-five menopausal women suffering from severe hot flushes and night sweats completed a 12-week intervention using this combination isoflavone nutritional supplement. RESULTS: We observed a 46% decrease in reported hot flushes, from an average of 9.7 to 5.2 per day. Quality of life, as assessed by the standardized Greene Questionnaire, showed similar improvement. Two markers of CVD risk, the ratio of total cholesterol to high-density lipoprotein (HDL) cholesterol and homocysteine, showed modest improvement. A proposed marker of breast cancer risk, the ratio of 2-hydroxyestrone to 16 alpha-hydroxyestrone, also showed a statistically significant improvement. CONCLUSIONS: The results of this pilot trial suggests that this combination isoflavone nutritional supplement may significantly relieve the most troubling symptoms of menopause, as well as confer some chemopreventive and cardioprotective benefits.

Adult↗
PubMed1986

Effect of continuous intraventricular estrogen or catechol estrogen treatment on catecholamine turnover in various brain regions.

The effect of 7-day i.v.t. administration of catechol estrogens (CE) or estrogens (5 micrograms/day) on the catecholamine turnover rate of various brain areas was examined in ovariectomized rats. Norepinephrine turnover was increased significantly in the hypothalamus and cerebral cortex by estradiol treatment but not by any CEs tested when compared to control values. However, the turnover rate of dopamine in the cerebral cortex was increased compared to control values only by the 2-hydroxyestrogens (2-hydroxyestradiol and 2-hydroxyestrone) and estradiol was without effect. Only estrogens and CEs with physiologically significant estrogen receptor binding affinities (17 beta-estradiol, moxestrol, 2-hydroxyestradiol and 4-hydroxyestradiol) decreased the turnover rate of dopamine in the corpus striatum compared to control values. Estrogens (17 alpha-estradiol and 2-hydroxyestrone) which are weak ligands for the estrogen receptor did not affect striatal dopamine turnover. In addition, body weight gain measured during estrogen treatment was reduced by CEs and estrogens which have significant estrogen receptor affinities. These results suggest that the CEs may play a role in central modulation of catecholaminergic function by estrogens either through direct actions of the catechol moiety or activation of estrogen receptors.

Animals↗
PubMed1995

Carcinogenic activities of various steroidal and nonsteroidal estrogens in the hamster kidney: relation to hormonal activity and cell proliferation.

The therapeutic use of estrogens has been associated with an increased risk of some of the most predominant, as well as less prevalent, cancers in women. The estrogen-induced renal tumor is one of the primary animal models to evaluate the carcinogenic properties of estrogens. Correlations were made with various estrogens by using parameters of estrogenicity end points such as competitive binding, progesterone receptor induction, and alterations in prolactin levels; in vitro renal proximal cell proliferation; and in vivo estrogen-induced carcinogenicity. The most potent estrogens were Moxestrol (MOX), diethylstilbestrol (DES), and 17 beta-estradiol, followed by indenestrol B, 16 alpha-hydroxyestrone, and 11 beta-methoxyestradiol with moderate estrogenic activities, whereas 11 beta-methylestradiol, 17 alpha-estradiol, indanestrol, and deoxoestrone were all relatively weaker. As expected, hydrolyzed Premarin (unconjugated estrogens) was strongly estrogenic. Of the estrogens tested, MOX was the most potent carcinogenic estrogen in the hamster kidney. Both 16 alpha-hydroxyestrone and 11 beta-methoxyestradiol induced intermediate tumor incidences with distinctly lower frequencies of renal tumor foci compared to the most potent carcinogenic estrogens. However, hamsters treated for 9.0 months with 11 beta-methylestradiol, 17 alpha-estradiol, deoxoestrone, and indanestrol exhibited no tumors. In contrast, treatment with estrone, equilin plus d-equilenin, and hydrolyzed Premarin for the same time period resulted in 100% renal tumor incidences and numerous tumor foci. Cell proliferation studies of cultured hamster kidney proximal tubule cells were carried out at varying estrogen concentrations (0.01-100 nM). Exposure to MOX resulted in consistently high renal cell proliferative response over a concentration range of 0.1-10 nM. Strongly carcinogenic estrogens such as estrone had a maximal renal cell proliferation response (2.4-fold above untreated control levels) between 0.1 and 10 nM, DES and 17 beta-estradiol responded at 1.0 nM, and 4-hydroxyestradiol responded at 10 nM. Interestingly, exposure to ethinylestradiol, a potent estrogen, at similar or higher doses as those used for DES and 17 beta-estradiol, yielded only a 10% renal tumor incidence and induced only a 1.7-fold increase in proximal tubule cell proliferation. In contrast, 17 alpha-estradiol, deoxoestrone, indanestrol, and 11 beta-methylestradiol, all weakly estrogenic and noncarcinogenic agents, had relatively little effect on tubule cell proliferation. The hydrolyzed Premarin exhibited a maximal 2.0-fold cell proliferative response at 10 nM. The present results provide clear evidence that, in the hamster kidney, the degree of carcinogenicity of a given estrogen correlates with its ability to induce proximal tubule cell proliferation in vitro.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1995

Natural estrogens induce modulation of microtubules in Chinese hamster V79 cells in culture.

Natural estrogens and their derivatives comprising 30 compounds in total were tested for their ability to induce microtubule disruption in Chinese hamster V79 cells. The cytoplasmic microtubule networks were examined by the indirect immunofluorescence method using anti-beta-tubulin antibody. The effective concentrations of 17 beta-estradiol (E2-17 beta) and 17 alpha-estradiol required for the induction of microtubule distribution in 50% of the cells (EC50) in 1 h were 10 and 9 microM for V79 cells, respectively, and 2-methoxyestradiol showed the strongest activity (EC50 2 microM) among the tested compounds including the catechol estrogens 2-hydroxyestradiol, 4-hydroxyestradiol, 2-hydroxyestrone, and 4-hydroxyestrone. The estrone series of estrogens showed relatively low activity for disruption of microtubule networks compared with E2-17 beta, whereas 3-deoxy-3-methylestradiol showed almost the same EC50 value as E2-17 beta. There was a correlation between the EC50 values of the compounds and their growth-inhibitory activities. The presence of 1 microM taxol in culture protected against 50 microM E2-17 beta-induced microtubule disruption. Cycloheximide and actinomycin D had no preventive action on the effect of E2-17 beta, suggesting that the microtubule-disruptive effect of E2-17 beta is not associated with newly synthesized proteins and mRNAs. The present results indicate that some natural estrogens cause microtubule disruption in a nongenomic manner.

Animals↗
PubMed1998

Effects of soy isoflavones on estrogen and phytoestrogen metabolism in premenopausal women.

Isoflavones and lignans are soy phytoestrogens that have been suggested to be anticarcinogenic. The mechanisms by which they exert cancer-preventive effects may involve modulation of estrogen synthesis and metabolism. To evaluate this hypothesis, a randomized, cross-over soy isoflavone feeding study was performed in 12 healthy premenopausal women. The study consisted of three diet periods, each separated by a washout of approximately 3 weeks. Each diet period lasted for three menstrual cycles plus 9 days (averaging approximately 100 days), during which subjects consumed their habitual diets supplemented with soy protein powder providing 0.16 (control diet), 1.01, or 2.01 mg of total isoflavones per kg of body weight per day (10+/-1.1, 65+/-9.4, or 129+/-16 mg/day, respectively). A 72-h urine sample was collected during the midfollicular phase (days 7-9) of the fourth menstrual cycle in each diet period. Urine samples were analyzed for 10 phytoestrogens and 15 endogenous estrogens and their metabolites by a capillary gas chromatography-mass spectrometry method. Urinary excretion of isoflavonoids and lignans significantly increased with increased isoflavone consumption. Compared with the control diet, increased isoflavone consumption decreased urinary excretion of estradiol, estrone, estriol, and total estrogens, as well as excretion of the hypothesized genotoxic estrogen metabolites, 16alpha-hydroxyestrone, 4-hydroxyestrone, and 4-hydroxyestradiol. Of importance are the observations of a significant increase in the 2-hydroxyestrone/16alpha-hydroxyestrone ratio and a decrease in the genotoxic/total estrogens ratio. These data suggest that soy isoflavone consumption may exert cancer-preventive effects by decreasing estrogen synthesis and altering metabolism away from genotoxic metabolites toward inactive metabolites.

Adult↗
PubMedDate not supplied

Determination of catechol and guaiacol estrogens in urine by capillary gas chromatography/mass spectrometry.

A gas chromatographic (GC)/mass spectrometric method for the simultaneous determination in urine of 2- and 4-hydroxyestrones and hydroxyestradiols, and their monomethyl ethers, is described. Separation of these catechol and guaiacol estrogens was achieved by derivatization into their trimethylsilyl and tert-butyldimethylsilyl ethers, followed by capillary GC on a DB-1 column. The calibration graphs were satisfactorily constructed for these estrogen metabolites by selected ion monitoring at the respective molecular ions using 2-bromoestrone and 4-hydroxyestradiol-d3 3-methyl ether as internal standards. The extraction and purification of the desired estrogens in biological fluids were effected by the combined use of Extrelut-3 and ion exchange columns. The sensitivity and reliability obtained by the newly developed method has proved to be satisfactory for the quantitation of catechol and guaiacol estrogens in human urine.

Estradiol↗
PubMed2007

Effects of a catechol-O-methyltransferase inhibitor on catechol estrogen-induced cellular transformation, chromosome aberrations and apoptosis in Syrian hamster embryo cells.

To examine a possible mechanism of endogenous estrogen-induced carcinogenesis, we studied the effect of the catechol-O-methyltransferase (COMT) inhibitor Ro 41-0960 on cell transforming and clastogenic activities of 2 catechol estrogens 2- and 4-hydroxyestrone (2- or 4-OHE1) using Syrian hamster embryo (SHE) cells. COMT activity was assayed by determining the methylation of 2- or 4-OHE1 using gas chromatography. The production of 2-methoxyestrone in cultures treated with 2-OHE1 was approximately 2-fold that of 4-methoxyestrone in cultures treated with 4-OHE1. 4-OHE1 induced morphological transformation at a higher frequency than 2-OHE1 did and the frequencies of cell transformation and chromosome aberrations were not significantly changed in cells treated with 4-OHE1 in the presence of Ro 41-0960. In contrast, the frequencies of cell transformation and chromosome aberrations were markedly increased in cells treated with 2-OHE1 along with Ro 41-0960 when compared to cells treated with 2-OHE1 alone. In addition, both catechol estrogens induced P53 protein expression and apoptosis. The frequencies of apoptotic cells induced by the catechol estrogens were modified by the COMT inhibition in a manner similar to those observed with the chromosome aberrations assay and the cell transformation assay, indicating that each effect by the catechol estrogens at the three measured endpoints might be caused by a mechanism similar to the others. Our findings indicate that COMT activity has an influence on cell transforming activity and its related genetic effects of catechol estrogens in SHE cells, which implies that an individual activity of COMT may be one of the etiological factors in endogenous estrogen-induced carcinogenesis.

Animals↗