catechol estrogen catechol estrogen a catechol estrogen is a steroidal estrogen that contains catechol (1,2-dihydroxybenzene) within its structure. the catechol estrogens are endogenous metabolites of estradiol and estrone and include the following compounds: 2-hydroxylated: 2-hydroxyestradiol 2-hydroxyestrone 2-hydroxyestriol 4-hydroxylated: 4-hydroxyestradiol 4-hydroxyestrone 4-hydroxyestriol structure of 2-hydroxyestradiol, a catechol estrogen. the most abundant catechol estrogen in serum and urine is 2-hydroxyestrone, with 2-hydroxyestradiol and 2-hydroxyestriol also being formed, while the principal 4-hydroxy catechol estrogen, 4-hydroxyestrone, is present in only small amounts in urine. 4-hydroxyestriol has been detected in the urine of pregnant women. the catechol estrogens are formed from estradiol and estrone by cytochrome p450 enzymes predominantly in the liver but also in extrahepatic tissues, and are metabolized by catechol o-methyltransferase (comt) into methoxylated estrogens such as 2-methoxyestradiol and 4-methoxyestrone as well as by conjugation via other phase ii enzymes. under poor conditions of inactivation by phase ii enzymes, catechol estrogens can undergo oxidation to reactive quinones and semiquinones, and this has been hypothesized to contribute to estrogen-induced carcinogenesis. similarly to estradiol and estrone, catechol estrogens possess estrogenic activity. 2-hydroxylated catechol estrogens are weak and possibly antiestrogenic estrogens, whereas their 4-hydroxylated counterparts are more potent in their estrogenic activity. for instance, 2-hydroxyestrone reportedly shows negligible uterotrophic effect in animals, whereas 4-hydroxy catechol estrogens show moderate changes in stimulating uterine weight. in addition to being substrates for comt similarly to catecholamines like dopamine, norepinephrine, and epinephrine, catechol estrogens are potent competitive inhibitors of comt as well as of tyrosine hydroxylase, and may affect both catecholamine biosynthesis and metabolism. affinities of estrogen receptor ligands for the erα and erβ ligandother namesrelative binding affinities (rba, %)aabsolute binding affinities (ki, nm)aaction erαerβerαerβ estradiole2; 17β-estradiol1001000.115 (0.04–0.24)0.15 (0.10–2.08)estrogen estronee1; 17-ketoestradiol16.39 (0.7–60)6.5 (1.36–52)0.445 (0.3–1.01)1.75 (0.35–9.24)estrogen estriole3; 16α-oh-17β-e212.65 (4.03–56)26 (14.0–44.6)0.45 (0.35–1.4)0.7 (0.63–0.7)estrogen estetrole4; 15α,16α-di-oh-17β-e24.03.04.919estrogen alfatradiol17α-estradiol20.5 (7–80.1)8.195 (2–42)0.2–0.520.43–1.2metabolite 16-epiestriol16β-hydroxy-17β-estradiol7.795 (4.94–63)50 ? ?metabolite 17-epiestriol16α-hydroxy-17α-estradiol55.45 (29–103)79–80 ? ?metabolite 16,17-epiestriol16β-hydroxy-17α-estradiol1.013 ? ?metabolite 2-hydroxyestradiol2-oh-e222 (7–81)11–352.51.3metabolite 2-methoxyestradiol2-meo-e20.0027–2.01.0 ? ?metabolite 4-hydroxyestradiol4-oh-e213 (8–70)7–561.01.9metabolite 4-methoxyestradiol4-meo-e22.01.0 ? ?metabolite 2-hydroxyestrone2-oh-e12.0–4.00.2–0.4 ? ?metabolite 2-methoxyestrone2-meo-e1<0.001–<1<1 ? ?metabolite 4-hydroxyestrone4-oh-e11.0–2.01.0 ? ?metabolite 4-methoxyestrone4-meo-e1<1<1 ? ?metabolite 16α-hydroxyestrone16α-oh-e1; 17-ketoestriol2.0–6.535 ? ?metabolite 2-hydroxyestriol2-oh-e32.01.0 ? ?metabolite 4-methoxyestriol4-meo-e31.01.0 ? ?metabolite estradiol sulfatee2s; estradiol 3-sulfate<1<1 ? ?metabolite estradiol disulfateestradiol 3,17β-disulfate0.0004 ? ? ?metabolite estradiol 3-glucuronidee2-3g0.0079 ? ? ?metabolite estradiol 17β-glucuronidee2-17g0.0015 ? ? ?metabolite estradiol 3-gluc. 17β-sulfatee2-3g-17s0.0001 ? ? ?metabolite estrone sulfatee1s; estrone 3-sulfate<1<1>10>10metabolite estradiol benzoateeb; estradiol 3-benzoate10 ? ? ?estrogen estradiol 17β-benzoatee2-17b11.332.6 ? ?estrogen estrone methyl etherestrone 3-methyl ether0.145 ? ? ?estrogen ent-estradiol1-estradiol1.31–12.349.44–80.07 ? ?estrogen equilin7-dehydroestrone13 (4.0–28.9)13.0–490.790.36estrogen equilenin6,8-didehydroestrone2.0–157.0–200.640.62estrogen 17β-dihydroequilin7-dehydro-17β-estradiol7.9–1137.9–1080.090.17estrogen 17α-dihydroequilin7-dehydro-17α-estradiol18.6 (18–41)14–320.240.57estrogen 17β-dihydroequilenin6,8-didehydro-17β-estradiol35–6890–1000.150.20estrogen 17α-dihydroequilenin6,8-didehydro-17α-estradiol20490.500.37estrogen δ8-estradiol8,9-dehydro-17β-estradiol68720.150.25estrogen δ8-estrone8,9-dehydroestrone19320.520.57estrogen ethinylestradiolee; 17α-ethynyl-17β-e2120.9 (68.8–480)44.4 (2.0–144)0.02–0.050.29–0.81estrogen mestranolee 3-methyl ether ?2.5 ? ?estrogen moxestrolru-2858; 11β-methoxy-ee35–435–200.52.6estrogen methylestradiol17α-methyl-17β-estradiol7044 ? ?estrogen diethylstilbestroldes; stilbestrol129.5 (89.1–468)219.63 (61.2–295)0.040.05estrogen hexestroldihydrodiethylstilbestrol153.6 (31–302)60–2340.060.06estrogen dienestroldehydrostilbestrol37 (20.4–223)56–4040.050.03estrogen benzestrol (b2)–114 ? ? ?estrogen chlorotrianisenetace1.74 ?15.30 ?estrogen triphenylethylenetpe0.074 ? ? ?estrogen triphenylbromoethylenetpbe2.69 ? ? ?estrogen tamoxifenici-46,4743 (0.1–47)3.33 (0.28–6)3.4–9.692.5serm afimoxifene4-hydroxytamoxifen; 4-oht100.1 (1.7–257)10 (0.98–339)2.3 (0.1–3.61)0.04–4.8serm toremifene4-chlorotamoxifen; 4-ct ? ?7.14–20.315.4serm clomifenemrl-4125 (19.2–37.2)120.91.2serm cyclofenilf-6066; sexovid151–152243 ? ?serm nafoxidineu-11,000a30.9–44160.30.8serm raloxifene–41.2 (7.8–69)5.34 (0.54–16)0.188–0.5220.2serm arzoxifenely-353,381 ? ?0.179 ?serm lasofoxifenecp-336,15610.2–16619.00.229 ?serm ormeloxifenecentchroman ? ?0.313 ?serm levormeloxifene6720-cdri; nnc-460,0201.551.88 ? ?serm ospemifenedeaminohydroxytoremifene0.82–2.630.59–1.22 ? ?serm bazedoxifene– ? ?0.053 ?serm etacstilgw-56384.3011.5 ? ?serm ici-164,384–63.5 (3.70–97.7)1660.20.08antiestrogen fulvestrantici-182,78043.5 (9.4–325)21.65 (2.05–40.5)0.421.3antiestrogen propylpyrazoletriolppt49 (10.0–89.1)0.120.4092.8erα agonist 16α-le216α-lactone-17β-estradiol14.6–570.0890.27131erα agonist 16α-iodo-e216α-iodo-17β-estradiol30.22.30 ? ?erα agonist methylpiperidinopyrazolempp110.05 ? ?erα antagonist diarylpropionitriledpn0.12–0.256.6–1832.41.7erβ agonist 8β-ve28β-vinyl-17β-estradiol0.3522.0–8312.90.50erβ agonist prinaberelerb-041; way-202,0410.2767–72 ? ?erβ agonist erb-196way-202,196 ?180 ? ?erβ agonist erteberelserba-1; ly-500,307 ? ?2.680.19erβ agonist serba-2– ? ?14.51.54erβ agonist coumestrol–9.225 (0.0117–94)64.125 (0.41–185)0.14–80.00.07–27.0xenoestrogen genistein–0.445 (0.0012–16)33.42 (0.86–87)2.6–1260.3–12.8xenoestrogen equol–0.2–0.2870.85 (0.10–2.85) ? ?xenoestrogen daidzein–0.07 (0.0018–9.3)0.7865 (0.04–17.1)2.085.3xenoestrogen biochanin a–0.04 (0.022–0.15)0.6225 (0.010–1.2)1748.9xenoestrogen kaempferol–0.07 (0.029–0.10)2.2 (0.002–3.00) ? ?xenoestrogen naringenin–0.0054 (<0.001–0.01)0.15 (0.11–0.33) ? ?xenoestrogen 8-prenylnaringenin8-pn4.4 ? ? ?xenoestrogen quercetin–<0.001–0.010.002–0.040 ? ?xenoestrogen ipriflavone–<0.01<0.01 ? ?xenoestrogen miroestrol–0.39 ? ? ?xenoestrogen deoxymiroestrol–2.0 ? ? ?xenoestrogen β-sitosterol–<0.001–0.0875<0.001–0.016 ? ?xenoestrogen resveratrol–<0.001–0.0032 ? ? ?xenoestrogen α-zearalenol–48 (13–52.5) ? ? ?xenoestrogen β-zearalenol–0.6 (0.032–13) ? ? ?xenoestrogen zeranolα-zearalanol48–111 ? ? ?xenoestrogen taleranolβ-zearalanol16 (13–17.8)140.80.9xenoestrogen zearalenonezen7.68 (2.04–28)9.45 (2.43–31.5) ? ?xenoestrogen zearalanonezan0.51 ? ? ?xenoestrogen bisphenol abpa0.0315 (0.008–1.0)0.135 (0.002–4.23)19535xenoestrogen endosulfaneds<0.001–<0.01<0.01 ? ?xenoestrogen keponechlordecone0.0069–0.2 ? ? ?xenoestrogen o,p'-ddt–0.0073–0.4 ? ? ?xenoestrogen p,p'-ddt–0.03 ? ? ?xenoestrogen methoxychlorp,p'-dimethoxy-ddt0.01 (<0.001–0.02)0.01–0.13 ? ?xenoestrogen hptehydroxychlor; p,p'-oh-ddt1.2–1.7 ? ? ?xenoestrogen testosteronet; 4-androstenolone<0.0001–<0.01<0.002–0.040>5000>5000androgen dihydrotestosteronedht; 5α-androstanolone0.01 (<0.001–0.05)0.0059–0.17221–>500073–1688androgen nandrolone19-nortestosterone; 19-nt0.010.2376553androgen dehydroepiandrosteronedhea; prasterone0.038 (<0.001–0.04)0.019–0.07245–1053163–515androgen 5-androstenediola5; androstenediol6173.60.9androgen 4-androstenediol–0.50.62319androgen 4-androstenedionea4; androstenedione<0.01<0.01>10000>10000androgen 3α-androstanediol3α-adiol0.070.326048androgen 3β-androstanediol3β-adiol3762androgen androstanedione5α-androstanedione<0.01<0.01>10000>10000androgen etiocholanedione5β-androstanedione<0.01<0.01>10000>10000androgen methyltestosterone17α-methyltestosterone<0.0001 ? ? ?androgen ethinyl-3α-androstanediol17α-ethynyl-3α-adiol4.0<0.07 ? ?estrogen ethinyl-3β-androstanediol17α-ethynyl-3β-adiol505.6 ? ?estrogen progesteronep4; 4-pregnenedione<0.001–0.6<0.001–0.010 ? ?progestogen norethisteronenet; 17α-ethynyl-19-nt0.085 (0.0015–<0.1)0.1 (0.01–0.3)1521084progestogen norethynodrel5(10)-norethisterone0.5 (0.3–0.7)<0.1–0.221453progestogen tibolone7α-methylnorethynodrel0.5 (0.45–2.0)0.2–0.076 ? ?progestogen δ4-tibolone7α-methylnorethisterone0.069–<0.10.027–<0.1 ? ?progestogen 3α-hydroxytibolone–2.5 (1.06–5.0)0.6–0.8 ? ?progestogen 3β-hydroxytibolone–1.6 (0.75–1.9)0.070–0.1 ? ?progestogen footnotes: a = (1) binding affinity values are of the format "median (range)" (# (#–#)), "range" (#–#), or "value" (#) depending on the values available. the full sets of values within the ranges can be found in the wiki code. (2) binding affinities were determined via displacement studies in a variety of in-vitro systems with labeled estradiol and human erα and erβ proteins (except the erβ values from kuiper et al. (1997), which are rat erβ). sources: see template page. selected biological properties of endogenous estrogens in rats estrogener rba (%)uterine weight (%)uterotrophylh levels (%)shbg rba (%) control–100–100– estradiol (e2)100506 ± 20+++12–19100 estrone (e1)11 ± 8490 ± 22+++ ?20 estriol (e3)10 ± 4468 ± 30+++8–183 estetrol (e4)0.5 ± 0.2 ?inactive ?1 17α-estradiol4.2 ± 0.8 ? ? ? ? 2-hydroxyestradiol24 ± 7285 ± 8+b31–6128 2-methoxyestradiol0.05 ± 0.04101inactive ?130 4-hydroxyestradiol45 ± 12 ? ? ? ? 4-methoxyestradiol1.3 ± 0.2260++ ?9 4-fluoroestradiola180 ± 43 ?+++ ? ? 2-hydroxyestrone1.9 ± 0.8130 ± 9inactive110–1428 2-methoxyestrone0.01 ± 0.00103 ± 7inactive95–100120 4-hydroxyestrone11 ± 4351++21–5035 4-methoxyestrone0.13 ± 0.04338++65–9212 16α-hydroxyestrone2.8 ± 1.0552 ± 42+++7–24<0.5 2-hydroxyestriol0.9 ± 0.3302+b ? ? 2-methoxyestriol0.01 ± 0.00 ?inactive ?4 notes: values are mean ± sd or range. er rba = relative binding affinity to estrogen receptors of rat uterine cytosol. uterine weight = percentage change in uterine wet weight of ovariectomized rats after 72 hours with continuous administration of 1 μg/hour via subcutaneously implanted osmotic pumps. lh levels = luteinizing hormone levels relative to baseline of ovariectomized rats after 24 to 72 hours of continuous administration via subcutaneous implant. footnotes: a = synthetic (i.e., not endogenous). b = atypical uterotrophic effect which plateaus within 48 hours (estradiol's uterotrophy continues linearly up to 72 hours). sources: see template.