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0 0 0 9 35 1 0 0 0 0 10 11 1 0 0 0 0 10 36 1 0 0 0 0 10 37 1 0 0 0 0 11 12 1 0 0 0 0 11 32 1 0 0 0 0 12 13 1 0 0 0 0 12 25 1 0 0 0 0 13 14 1 0 0 0 0 13 38 1 0 0 0 0 13 39 1 0 0 0 0 14 15 1 0 0 0 0 14 40 1 0 0 0 0 14 41 1 0 0 0 0 15 16 4 0 0 0 0 15 21 4 0 0 0 0 16 17 4 0 0 0 0 16 42 1 0 0 0 0 17 18 1 0 0 0 0 17 19 4 0 0 0 0 18 43 1 0 0 0 0 19 20 4 0 0 0 0 19 44 1 0 0 0 0 20 21 4 0 0 0 0 20 45 1 0 0 0 0 M END): 16 ms reading 45 atoms ModelSet: haveSymmetry:false haveUnitcells:false haveFractionalCoord:false 1 model in this collection. 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| 17α-Epiestriol, or simply 17-epiestriol, also known as 16α-hydroxy-17α-estradiol or estra-1,3,5(10)-triene-3,16α,17α-triol, is a minor and weak endogenous estrogen, and the 17α-epimer of estriol (which is 16α-hydroxy-17β-estradiol). It is formed from 16α-hydroxyestrone. In contrast to other endogenous estrogens like estradiol, 17α-epiestriol is a selective agonist of the ERβ. It is described as a relatively weak estrogen, which is in accordance with its relatively low affinity for the ERα. 17α-Epiestriol has been found to be approximately 400-fold more potent than estradiol in inhibiting tumor necrosis factor α (TNFα)-induced vascular cell adhesion molecule 1 (VCAM-1) expression in vitro. |
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Read full article at Wikipedia
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InChI=1S/C18H24O3/c1- 18-7-6-13-12-5-3-11(19)8-10(12)2-4-14(13)15(18)9-16(20)17(18)21/h3,5,8,13-17,19-21H,2,4,6-7,9H2,1H3/t13-,14-,15+,16-,17-,18+/m1/s1 |
| PROQIPRRNZUXQM-PNVOZDDCSA-N |
| C12=CC=C(C=C1CC[C@@]3([C@@]2(CC[C@]4([C@]3(C[C@H]([C@H]4O)O)[H])C)[H])[H])O |
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estrogen receptor agonist
An agonist at the estrogen receptor.
human urinary metabolite
Any metabolite (endogenous or exogenous) found in human urine samples.
estrogen
A hormone that stimulates or controls the development and maintenance of female sex characteristics in mammals by binding to oestrogen receptors. The oestrogens are named for their importance in the oestrous cycle. The oestrogens that occur naturally in the body, notably estrone, estradiol, estriol, and estetrol are steroids. Other compounds with oestrogenic activity are produced by plants (phytoestrogens) and fungi (mycoestrogens); synthetic compounds with oestrogenic activity are known as xenoestrogens.
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View more via ChEBI Ontology
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estra-1(10),2,4-triene-3,16α,17α-triol
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(16α,17α)-estra-1(10),2,4-triene-3,16,17-triol
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IUPAC
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(8R,9S,13S,14S,16R,17S)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthrene-3,16,17-triol
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IUPAC
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1,3,5(10)-estratriene-3,16α,17α-triol
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ChEBI
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16α,17α-estriol
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UniProt
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16α-hydroxy-17α-estradiol
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ChEBI
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17-epiestriol
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LIPID MAPS
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17α-estriol
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ChemIDplus
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3,16α,17α-trihydroxy-1,3,5(10)-estratriene
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ChEBI
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1228-72-4
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CAS Registry Number
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ChemIDplus
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2622737
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Reaxys Registry Number
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Reaxys
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Sood D, Johnson N, Jain P, Siskos AP, Bennett M, Gilham C, Busana MC, Peto J, Dos-Santos-Silva I, Keun HC, Fletcher O (2017)
CYP3A7*1C allele is associated with reduced levels of 2-hydroxylation pathway oestrogen metabolites.
British journal of cancer 116, 382-388 [PubMed:28072767]
[show Abstract]
BackgroundEndogenous sex hormones are well-established risk factors for breast cancer; the contribution of specific oestrogen metabolites (EMs) and/or ratios of specific EMs is less clear. We have previously identified a CYP3A7*1C allele that is associated with lower urinary oestrone (E1) levels in premenopausal women. The purpose of this analysis was to determine whether this allele was associated with specific pathway EMs.MethodsWe measured successfully 12 EMs in mid-follicular phase urine samples from 30 CYP3A7*1C carriers and 30 non-carriers using HPLC-MS/MS.ResultsIn addition to having lower urinary E1 levels, CYP3A7*1C carriers had significantly lower levels of four of the 2-hydroxylation pathway EMs that we measured (2-hydroxyestrone, P=1.1 × 10-12; 2-hydroxyestradiol, P=2.7 × 10-7; 2-methoxyestrone, P=1.9 × 10-12; and 2-methoxyestradiol, P=0.0009). By contrast, 16α-hydroxylation pathway EMs were slightly higher in carriers and significantly so for 17-epiestriol (P=0.002).ConclusionsThe CYP3A7*1C allele is associated with a lower urinary E1 levels, a more pronounced reduction in 2-hydroxylation pathway EMs and a lower ratio of 2-hydroxylation:16α-hydroxylation EMs in premenopausal women. To further characterise the association between parent oestrogens, EMs and subsequent risk of breast cancer, characterisation of additional genetic variants that influence oestrogen metabolism and large prospective studies of a broad spectrum of EMs will be required. | Dallal CM, Brinton LA, Matthews CE, Pfeiffer RM, Hartman TJ, Lissowska J, Falk RT, Garcia-Closas M, Xu X, Veenstra TD, Gierach GL (2016)
Association of Active and Sedentary Behaviors with Postmenopausal Estrogen Metabolism.
Medicine and science in sports and exercise 48, 439-448 [PubMed:26460631]
[show Abstract]
PurposePhysical activity may reduce endogenous estrogens, but few studies have assessed effects on estrogen metabolism and none have evaluated sedentary behavior in relation to estrogen metabolism. We assessed relationships between accelerometer-measured physical activity and sedentary behavior and 15 urinary estrogens and estrogen metabolites (EM) among postmenopausal controls from a population-based breast cancer case-control study conducted in Poland (2000-2003).MethodsPostmenopausal women (N = 542) were ages 40 to 72 yr and not currently using hormone therapy. Accelerometers, worn for 7 d, were used to derive measures of average activity (counts per day) and sedentary behavior (<100 counts per minute per day). Estrogen metabolites were measured in 12-h urine samples using liquid chromatography-tandem mass spectrometry. Estrogen metabolites were analyzed individually, in metabolic pathways (C-2, -4, or -16), and as ratios relative to parent estrogens. Geometric means of estrogen metabolites by tertiles of accelerometer-measures, adjusted for age and body mass, were computed using linear models.ResultsHigh activity was associated with lower levels of estrone and estradiol (P trend = 0.01), whereas increased sedentary time was positively associated with these parent estrogens (P trend = 0.04). Inverse associations were observed between high activity and 2-methoxyestradiol, 4-methoxyestradiol, 17-epiestriol, and 16-epiestriol (P trend = 0.03). Sedentary time was positively associated with methylated catechols in the 2- and 4-hydroxylation pathways (P trend ≤ 0.04). Women in the highest tertile of activity had increased hydroxylation at the C-2, -4, and -16 sites relative to parent estrogens (P trend ≤ 0.02), whereas increased sedentary time was associated with a lower 16-pathway/parent estrogen ratio (P trend = 0.01).ConclusionsHigher activity was associated with lower urinary estrogens, possibly through increased estrogen hydroxylation and subsequent metabolism, whereas sedentary behavior may reduce metabolism. | Sisti JS, Hankinson SE, Caporaso NE, Gu F, Tamimi RM, Rosner B, Xu X, Ziegler R, Eliassen AH (2015)
Caffeine, coffee, and tea intake and urinary estrogens and estrogen metabolites in premenopausal women.
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 24, 1174-1183 [PubMed:26063478]
[show Abstract]
BackgroundPrior studies have found weak inverse associations between breast cancer and caffeine and coffee intake, possibly mediated through their effects on sex hormones.MethodsHigh-performance liquid chromatography/tandem mass spectrometry was used to quantify levels of 15 individual estrogens and estrogen metabolites (EM) among 587 premenopausal women in the Nurses' Health Study II with mid-luteal phase urine samples and caffeine, coffee, and/or tea intakes from self-reported food frequency questionnaires. Multivariate linear mixed models were used to estimate geometric means of individual EM, pathways, and ratios by intake categories, and P values for tests of linear trend.ResultsCompared with women in the lowest quartile of caffeine consumption, those in the top quartile had higher urinary concentrations of 16α-hydroxyestrone (28% difference; Ptrend = 0.01) and 16-epiestriol (13% difference; Ptrend = 0.04), and a decreased parent estrogens/2-, 4-, 16-pathway ratio (Ptrend = 0.03). Coffee intake was associated with higher 2-catechols, including 2-hydroxyestradiol (57% difference, ≥4 cups/day vs. ≤6 cups/week; Ptrend = 0.001) and 2-hydroxyestrone (52% difference; Ptrend = 0.001), and several ratio measures. Decaffeinated coffee was not associated with 2-pathway metabolism, but women in the highest (vs. lowest) category of intake (≥2 cups/day vs. ≤1-3 cups/month) had significantly lower levels of two 16-pathway metabolites, estriol (25% difference; Ptrend = 0.01) and 17-epiestriol (48% difference; Ptrend = 0.0004). Tea intake was positively associated with 17-epiestriol (52% difference; Ptrend = 0.01).ConclusionCaffeine and coffee intake were both associated with profiles of estrogen metabolism in premenopausal women.ImpactConsumption of caffeine and coffee may alter patterns of premenopausal estrogen metabolism. | Falk RT, Dallal CM, Lacey JV, Bauer DC, Buist DS, Cauley JA, Hue TF, LaCroix AZ, Tice JA, Pfeiffer RM, Xu X, Veenstra TD, Brinton LA, B∼FIT Research Group (2015)
Estrogen Metabolites Are Not Associated with Colorectal Cancer Risk in Postmenopausal Women.
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 24, 1419-1422 [PubMed:26104910]
[show Abstract]
BackgroundA potential protective role for estrogen in colon carcinogenesis has been suggested based on exogenous hormone use, but it is unclear from previous studies whether endogenous estrogens are related to colorectal cancer risk. These few prior studies focused on parent estrogens; none evaluated effects of estrogen metabolism in postmenopausal women.MethodsWe followed 15,595 women (ages 55-80 years) enrolled in the Breast and Bone Follow-up to the Fracture Intervention Trial (B∼FIT) who donated blood between 1992 and 1993 for cancer through December 2004. A panel of 15 estrogen metabolites (EM), including estradiol and estrone, were measured in serum from 187 colorectal cancer cases and a subcohort of 501 women not using exogenous hormones at blood draw. We examined EM individually, grouped by pathway (hydroxylation at the C-2, C-4, or C-16 position) and by ratios of the groupings using Cox proportional hazards regression models.ResultsNo significant associations were seen for estrone (HRQ4 vs. Q1 = 1.15; 95% CI, 0.69-1.93; Ptrend = 0.54), estradiol (HRQ4 vs. Q1 = 0.98; 95% CI, 0.58-1.64; Ptrend > 0.99), or total EM (the sum of all EM; HRQ4 vs. Q1 = 1.35; 95% CI, 0.81-2.24; Ptrend = 0.33). Most metabolites in the 2-, 4-, or 16-pathway were unrelated to risk, although a borderline trend in risk was associated with high levels of 17-epiestriol.ConclusionCirculating estrogens and their metabolites were generally unrelated to colorectal cancer risk in postmenopausal women.ImpactAdditional studies are needed to understand how exogenous estrogen may prevent colorectal cancer. | Oh H, Smith-Warner SA, Tamimi RM, Wang M, Xu X, Hankinson SE, Fuhrman BJ, Ziegler RG, Eliassen AH (2015)
Dietary Fat and Fiber Intakes Are Not Associated with Patterns of Urinary Estrogen Metabolites in Premenopausal Women.
The Journal of nutrition 145, 2109-2116 [PubMed:26180245]
[show Abstract]
BackgroundInterindividual differences in the bioavailability of potentially carcinogenic estrogen and estrogen metabolites (EMs) may play a role in the risk of breast cancer.ObjectiveWe examined whether dietary intakes of fiber and fat influence premenopausal EM profiles through effects on estrogen synthesis, metabolism, or excretion.MethodsWe conducted a cross-sectional analysis of 598 premenopausal women who participated in a reproducibility study (n = 109) or served as controls in a nested case-control study of breast cancer (n = 489) within the Nurses' Health Study II. Dietary intakes of fiber and fat were assessed via semiquantitative food frequency questionnaires in 1995 and 1999. Midluteal urine samples were collected between 1996 and 1999 and EMs were quantified with the use of HPLC-tandem mass spectrometry. Linear mixed models were used to estimate creatinine-adjusted geometric means for individual EMs and their pathway groups across categories of dietary intake while controlling for total energy intake and potential confounders.ResultsHigher total dietary fiber intake (>25 g/d vs. ≤15 g/d) was associated with significantly higher concentrations of 4-methoxyestradiol (50% difference, P-difference = 0.01, P-trend = 0.004) and lower concentrations of 17-epiestriol (-27% difference, P-difference = 0.03, P-trend = 0.03), but was not associated with any other EMs. The associations did not vary by fiber intake from different sources. Total fat intake (>35% energy vs. ≤25% energy) was suggestively positively associated with 17-epiestriol (22.6% difference, P-difference = 0.14, P-trend = 0.06); the association was significant for polyunsaturated fatty acid (37% difference, P-difference = 0.01, P-trend = 0.01) and trans fat (36.1% difference, P-difference = 0.01, P-trend = 0.01) intakes.ConclusionFiber and fat intakes were not strongly associated with patterns of estrogen metabolism in premenopausal women. Our data suggest estrogen metabolism is not a major mechanism through which dietary fiber and fat may affect breast or other hormone-related cancer risks. | Sneitz N, Vahermo M, Mosorin J, Laakkonen L, Poirier D, Finel M (2013)
Regiospecificity and stereospecificity of human UDP-glucuronosyltransferases in the glucuronidation of estriol, 16-epiestriol, 17-epiestriol, and 13-epiestradiol.
Drug metabolism and disposition: the biological fate of chemicals 41, 582-591 [PubMed:23288867]
[show Abstract]
The glucuronidation of estriol, 16-epiestriol, and 17-epiestriol by the human UDP-glucuronosyltransferases (UGTs) of subfamilies 1A, 2A, and 2B was examined. UGT1A10 is highly active in the conjugation of the 3-OH in all these estriols, whereas UGT2B7 is the most active UGT toward one of the ring D hydroxyls, the 16-OH in estriol and 16-epiestriol, but the 17-OH in 17-epiestriol. Kinetic analyses indicated that the 17-OH configuration plays a major role in the affinity of UGT2B7 for estrogens. The glucuronidation of the different estriols by the human liver and intestine microsomes reflects the activity of UGT1A10 and UGT2B7 in combination with the tissues' difference in UGT1A10 expression. The UGT1A10 mutant 1A10-F93G exhibited much higher V(max) values than UGT1A10 in estriol and 17-epiestriol glucuronidation, but a significantly lower value in 16-epiestriol glucuronidation. To this study on estriol glucuronidation we have added experiments with 13-epiestradiol, a synthetic estradiol in which the spatial arrangement of the methyl on C18 and the hydroxyl on C17 is significantly different than in other estrogens. In comparison with estradiol glucuronidation, the C13 configuration change decreases the turnover of UGTs that conjugate the 3-OH, but increases it in UGTs that primarily conjugate the 17-OH. Unexpectedly, UGT2B17 exhibited similar conjugation rates of both the 17-OH and 3-OH of 13-espiestradiol. The combined results reveal the strong preference of UGT1A10 for the 3-OH of physiologic estrogens and the equivalently strong preference of UGT2B7 and UGT2B17 for the hydroxyls on ring D of such steroid hormones. | Mukherjee TK, Nathan L, Dinh H, Reddy ST, Chaudhuri G (2003)
17-epiestriol, an estrogen metabolite, is more potent than estradiol in inhibiting vascular cell adhesion molecule 1 (VCAM-1) mRNA expression.
The Journal of biological chemistry 278, 11746-11752 [PubMed:12547825]
[show Abstract]
17-beta estradiol (17-beta E(2)) attenuates the expression of vascular cell adhesion molecule 1 (VCAM-1) in vivo at physiological levels (pg/ml), whereas supraphysiological concentrations of 17-beta E(2) (ng/ml) are required in vitro. We assessed whether a metabolite of estrogen, which could only be generated in vivo, might be a more potent inhibitor of VCAM-1 expression and thereby explain this discrepancy. We report here that 17-epiestriol, an estrogen metabolite and a selective estrogen receptor (ER) beta agonist, is approximately 400x more potent than 17-beta E(2) in suppressing tumor necrosis factor (TNF) alpha-induced VCAM-1 mRNA as well as protein expression in human umbilical vein endothelial cells. Genistein, an ERbeta agonist, at low concentrations (1 and 10 nm) also suppressed TNFalpha-induced VCAM-1 mRNA expression. These actions of 17-epiestriol and genistein were significantly attenuated in the presence of the estrogen receptor antagonist ICI-182780. Other estrogenic compounds such as ethinyl estradiol and estrone did not have any effect on TNFalpha-induced VCAM-1 expression at the concentrations tested. We further show that, 1) 17-epiestriol induces the expression of endothelial nitric-oxide synthase mRNA and protein, 2) 17-epiestriol prevents TNFalpha-induced migration of NFkappaB into the nucleus, 3) N(G)-nitro-l-arginine methyl ester, an inhibitor of NO synthesis, abolishes 17-epiestriol-mediated inhibition of TNFalpha-induced VCAM-1 expression and migration of NFkappaB from the cytoplasm to the nucleus. Our results indicate that 17-epiestriol is more potent than 17-beta E(2) in suppressing TNFalpha-induced VCAM-1 expression and that this action is modulated at least in part through NO. |
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