Global InformationCatechol estrogen information
A catechol estrogen is a steroidal estrogen that contains catechol (1,2-dihydroxybenzene) within its structure.[1] The catechol estrogens are endogenous metabolites of estradiol and estrone and include the following compounds:[1][2]
- 2-Hydroxylated:
- 2-Hydroxyestradiol
- 2-Hydroxyestrone
- 2-Hydroxyestriol
- 4-Hydroxylated:
- 4-Hydroxyestradiol
- 4-Hydroxyestrone
- 4-Hydroxyestriol
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.[1] 4-Hydroxyestriol has been detected in the urine of pregnant women.[3] 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.[1][2] 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.[2]
Similarly to estradiol and estrone, catechol estrogens possess estrogenic activity.[1] 2-Hydroxylated catechol estrogens are weak and possibly antiestrogenic estrogens, whereas their 4-hydroxylated counterparts are more potent in their estrogenic activity.[1] For instance, 2-hydroxyestrone reportedly shows negligible uterotrophic effect in animals, whereas 4-hydroxy catechol estrogens show moderate changes in stimulating uterine weight.[1] 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.[1][2]
| Ligand | Other names | Relative binding affinities (RBA, %)a | Absolute binding affinities (Ki, nM)a | Action | ||
|---|---|---|---|---|---|---|
| ERα | ERβ | ERα | ERβ | |||
| Estradiol | E2; 17β-Estradiol | 100 | 100 | 0.115 (0.04–0.24) | 0.15 (0.10–2.08) | Estrogen |
| Estrone | E1; 17-Ketoestradiol | 16.39 (0.7–60) | 6.5 (1.36–52) | 0.445 (0.3–1.01) | 1.75 (0.35–9.24) | Estrogen |
| Estriol | E3; 16α-OH-17β-E2 | 12.65 (4.03–56) | 26 (14.0–44.6) | 0.45 (0.35–1.4) | 0.7 (0.63–0.7) | Estrogen |
| Estetrol | E4; 15α,16α-Di-OH-17β-E2 | 4.0 | 3.0 | 4.9 | 19 | Estrogen |
| Alfatradiol | 17α-Estradiol | 20.5 (7–80.1) | 8.195 (2–42) | 0.2–0.52 | 0.43–1.2 | Metabolite |
| 16-Epiestriol | 16β-Hydroxy-17β-estradiol | 7.795 (4.94–63) | 50 | ? | ? | Metabolite |
| 17-Epiestriol | 16α-Hydroxy-17α-estradiol | 55.45 (29–103) | 79–80 | ? | ? | Metabolite |
| 16,17-Epiestriol | 16β-Hydroxy-17α-estradiol | 1.0 | 13 | ? | ? | Metabolite |
| 2-Hydroxyestradiol | 2-OH-E2 | 22 (7–81) | 11–35 | 2.5 | 1.3 | Metabolite |
| 2-Methoxyestradiol | 2-MeO-E2 | 0.0027–2.0 | 1.0 | ? | ? | Metabolite |
| 4-Hydroxyestradiol | 4-OH-E2 | 13 (8–70) | 7–56 | 1.0 | 1.9 | Metabolite |
| 4-Methoxyestradiol | 4-MeO-E2 | 2.0 | 1.0 | ? | ? | Metabolite |
| 2-Hydroxyestrone | 2-OH-E1 | 2.0–4.0 | 0.2–0.4 | ? | ? | Metabolite |
| 2-Methoxyestrone | 2-MeO-E1 | <0.001–<1 | <1 | ? | ? | Metabolite |
| 4-Hydroxyestrone | 4-OH-E1 | 1.0–2.0 | 1.0 | ? | ? | Metabolite |
| 4-Methoxyestrone | 4-MeO-E1 | <1 | <1 | ? | ? | Metabolite |
| 16α-Hydroxyestrone | 16α-OH-E1; 17-Ketoestriol | 2.0–6.5 | 35 | ? | ? | Metabolite |
| 2-Hydroxyestriol | 2-OH-E3 | 2.0 | 1.0 | ? | ? | Metabolite |
| 4-Methoxyestriol | 4-MeO-E3 | 1.0 | 1.0 | ? | ? | Metabolite |
| Estradiol sulfate | E2S; Estradiol 3-sulfate | <1 | <1 | ? | ? | Metabolite |
| Estradiol disulfate | Estradiol 3,17β-disulfate | 0.0004 | ? | ? | ? | Metabolite |
| Estradiol 3-glucuronide | E2-3G | 0.0079 | ? | ? | ? | Metabolite |
| Estradiol 17β-glucuronide | E2-17G | 0.0015 | ? | ? | ? | Metabolite |
| Estradiol 3-gluc. 17β-sulfate | E2-3G-17S | 0.0001 | ? | ? | ? | Metabolite |
| Estrone sulfate | E1S; Estrone 3-sulfate | <1 | <1 | >10 | >10 | Metabolite |
| Estradiol benzoate | EB; Estradiol 3-benzoate | 10 | ? | ? | ? | Estrogen |
| Estradiol 17β-benzoate | E2-17B | 11.3 | 32.6 | ? | ? | Estrogen |
| Estrone methyl ether | Estrone 3-methyl ether | 0.145 | ? | ? | ? | Estrogen |
| ent-Estradiol | 1-Estradiol | 1.31–12.34 | 9.44–80.07 | ? | ? | Estrogen |
| Equilin | 7-Dehydroestrone | 13 (4.0–28.9) | 13.0–49 | 0.79 | 0.36 | Estrogen |
| Equilenin | 6,8-Didehydroestrone | 2.0–15 | 7.0–20 | 0.64 | 0.62 | Estrogen |
| 17β-Dihydroequilin | 7-Dehydro-17β-estradiol | 7.9–113 | 7.9–108 | 0.09 | 0.17 | Estrogen |
| 17α-Dihydroequilin | 7-Dehydro-17α-estradiol | 18.6 (18–41) | 14–32 | 0.24 | 0.57 | Estrogen |
| 17β-Dihydroequilenin | 6,8-Didehydro-17β-estradiol | 35–68 | 90–100 | 0.15 | 0.20 | Estrogen |
| 17α-Dihydroequilenin | 6,8-Didehydro-17α-estradiol | 20 | 49 | 0.50 | 0.37 | Estrogen |
| Δ8-Estradiol | 8,9-Dehydro-17β-estradiol | 68 | 72 | 0.15 | 0.25 | Estrogen |
| Δ8-Estrone | 8,9-Dehydroestrone | 19 | 32 | 0.52 | 0.57 | Estrogen |
| Ethinylestradiol | EE; 17α-Ethynyl-17β-E2 | 120.9 (68.8–480) | 44.4 (2.0–144) | 0.02–0.05 | 0.29–0.81 | Estrogen |
| Mestranol | EE 3-methyl ether | ? | 2.5 | ? | ? | Estrogen |
| Moxestrol | RU-2858; 11β-Methoxy-EE | 35–43 | 5–20 | 0.5 | 2.6 | Estrogen |
| Methylestradiol | 17α-Methyl-17β-estradiol | 70 | 44 | ? | ? | Estrogen |
| Diethylstilbestrol | DES; Stilbestrol | 129.5 (89.1–468) | 219.63 (61.2–295) | 0.04 | 0.05 | Estrogen |
| Hexestrol | Dihydrodiethylstilbestrol | 153.6 (31–302) | 60–234 | 0.06 | 0.06 | Estrogen |
| Dienestrol | Dehydrostilbestrol | 37 (20.4–223) | 56–404 | 0.05 | 0.03 | Estrogen |
| Benzestrol (B2) | – | 114 | ? | ? | ? | Estrogen |
| Chlorotrianisene | TACE | 1.74 | ? | 15.30 | ? | Estrogen |
| Triphenylethylene | TPE | 0.074 | ? | ? | ? | Estrogen |
| Triphenylbromoethylene | TPBE | 2.69 | ? | ? | ? | Estrogen |
| Tamoxifen | ICI-46,474 | 3 (0.1–47) | 3.33 (0.28–6) | 3.4–9.69 | 2.5 | SERM |
| Afimoxifene | 4-Hydroxytamoxifen; 4-OHT | 100.1 (1.7–257) | 10 (0.98–339) | 2.3 (0.1–3.61) | 0.04–4.8 | SERM |
| Toremifene | 4-Chlorotamoxifen; 4-CT | ? | ? | 7.14–20.3 | 15.4 | SERM |
| Clomifene | MRL-41 | 25 (19.2–37.2) | 12 | 0.9 | 1.2 | SERM |
| Cyclofenil | F-6066; Sexovid | 151–152 | 243 | ? | ? | SERM |
| Nafoxidine | U-11,000A | 30.9–44 | 16 | 0.3 | 0.8 | SERM |
| Raloxifene | – | 41.2 (7.8–69) | 5.34 (0.54–16) | 0.188–0.52 | 20.2 | SERM |
| Arzoxifene | LY-353,381 | ? | ? | 0.179 | ? | SERM |
| Lasofoxifene | CP-336,156 | 10.2–166 | 19.0 | 0.229 | ? | SERM |
| Ormeloxifene | Centchroman | ? | ? | 0.313 | ? | SERM |
| Levormeloxifene | 6720-CDRI; NNC-460,020 | 1.55 | 1.88 | ? | ? | SERM |
| Ospemifene | Deaminohydroxytoremifene | 0.82–2.63 | 0.59–1.22 | ? | ? | SERM |
| Bazedoxifene | – | ? | ? | 0.053 | ? | SERM |
| Etacstil | GW-5638 | 4.30 | 11.5 | ? | ? | SERM |
| ICI-164,384 | – | 63.5 (3.70–97.7) | 166 | 0.2 | 0.08 | Antiestrogen |
| Fulvestrant | ICI-182,780 | 43.5 (9.4–325) | 21.65 (2.05–40.5) | 0.42 | 1.3 | Antiestrogen |
| Propylpyrazoletriol | PPT | 49 (10.0–89.1) | 0.12 | 0.40 | 92.8 | ERα agonist |
| 16α-LE2 | 16α-Lactone-17β-estradiol | 14.6–57 | 0.089 | 0.27 | 131 | ERα agonist |
| 16α-Iodo-E2 | 16α-Iodo-17β-estradiol | 30.2 | 2.30 | ? | ? | ERα agonist |
| Methylpiperidinopyrazole | MPP | 11 | 0.05 | ? | ? | ERα antagonist |
| Diarylpropionitrile | DPN | 0.12–0.25 | 6.6–18 | 32.4 | 1.7 | ERβ agonist |
| 8β-VE2 | 8β-Vinyl-17β-estradiol | 0.35 | 22.0–83 | 12.9 | 0.50 | ERβ agonist |
| Prinaberel | ERB-041; WAY-202,041 | 0.27 | 67–72 | ? | ? | ERβ agonist |
| ERB-196 | WAY-202,196 | ? | 180 | ? | ? | ERβ agonist |
| Erteberel | SERBA-1; LY-500,307 | ? | ? | 2.68 | 0.19 | ERβ agonist |
| SERBA-2 | – | ? | ? | 14.5 | 1.54 | ERβ agonist |
| Coumestrol | – | 9.225 (0.0117–94) | 64.125 (0.41–185) | 0.14–80.0 | 0.07–27.0 | Xenoestrogen |
| Genistein | – | 0.445 (0.0012–16) | 33.42 (0.86–87) | 2.6–126 | 0.3–12.8 | Xenoestrogen |
| Equol | – | 0.2–0.287 | 0.85 (0.10–2.85) | ? | ? | Xenoestrogen |
| Daidzein | – | 0.07 (0.0018–9.3) | 0.7865 (0.04–17.1) | 2.0 | 85.3 | Xenoestrogen |
| Biochanin A | – | 0.04 (0.022–0.15) | 0.6225 (0.010–1.2) | 174 | 8.9 | Xenoestrogen |
| 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-Prenylnaringenin | 8-PN | 4.4 | ? | ? | ? | Xenoestrogen |
| Quercetin | – | <0.001–0.01 | 0.002–0.040 | ? | ? | 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 |
| Zeranol | α-Zearalanol | 48–111 | ? | ? | ? | Xenoestrogen |
| Taleranol | β-Zearalanol | 16 (13–17.8) | 14 | 0.8 | 0.9 | Xenoestrogen |
| Zearalenone | ZEN | 7.68 (2.04–28) | 9.45 (2.43–31.5) | ? | ? | Xenoestrogen |
| Zearalanone | ZAN | 0.51 | ? | ? | ? | Xenoestrogen |
| Bisphenol A | BPA | 0.0315 (0.008–1.0) | 0.135 (0.002–4.23) | 195 | 35 | Xenoestrogen |
| Endosulfan | EDS | <0.001–<0.01 | <0.01 | ? | ? | Xenoestrogen |
| Kepone | Chlordecone | 0.0069–0.2 | ? | ? | ? | Xenoestrogen |
| o,p'-DDT | – | 0.0073–0.4 | ? | ? | ? | Xenoestrogen |
| p,p'-DDT | – | 0.03 | ? | ? | ? | Xenoestrogen |
| Methoxychlor | p,p'-Dimethoxy-DDT | 0.01 (<0.001–0.02) | 0.01–0.13 | ? | ? | Xenoestrogen |
| HPTE | Hydroxychlor; p,p'-OH-DDT | 1.2–1.7 | ? | ? | ? | Xenoestrogen |
| Testosterone | T; 4-Androstenolone | <0.0001–<0.01 | <0.002–0.040 | >5000 | >5000 | Androgen |
| Dihydrotestosterone | DHT; 5α-Androstanolone | 0.01 (<0.001–0.05) | 0.0059–0.17 | 221–>5000 | 73–1688 | Androgen |
| Nandrolone | 19-Nortestosterone; 19-NT | 0.01 | 0.23 | 765 | 53 | Androgen |
| Dehydroepiandrosterone | DHEA; Prasterone | 0.038 (<0.001–0.04) | 0.019–0.07 | 245–1053 | 163–515 | Androgen |
| 5-Androstenediol | A5; Androstenediol | 6 | 17 | 3.6 | 0.9 | Androgen |
| 4-Androstenediol | – | 0.5 | 0.6 | 23 | 19 | Androgen |
| 4-Androstenedione | A4; Androstenedione | <0.01 | <0.01 | >10000 | >10000 | Androgen |
| 3α-Androstanediol | 3α-Adiol | 0.07 | 0.3 | 260 | 48 | Androgen |
| 3β-Androstanediol | 3β-Adiol | 3 | 7 | 6 | 2 | Androgen |
| Androstanedione | 5α-Androstanedione | <0.01 | <0.01 | >10000 | >10000 | Androgen |
| Etiocholanedione | 5β-Androstanedione | <0.01 | <0.01 | >10000 | >10000 | Androgen |
| Methyltestosterone | 17α-Methyltestosterone | <0.0001 | ? | ? | ? | Androgen |
| Ethinyl-3α-androstanediol | 17α-Ethynyl-3α-adiol | 4.0 | <0.07 | ? | ? | Estrogen |
| Ethinyl-3β-androstanediol | 17α-Ethynyl-3β-adiol | 50 | 5.6 | ? | ? | Estrogen |
| Progesterone | P4; 4-Pregnenedione | <0.001–0.6 | <0.001–0.010 | ? | ? | Progestogen |
| Norethisterone | NET; 17α-Ethynyl-19-NT | 0.085 (0.0015–<0.1) | 0.1 (0.01–0.3) | 152 | 1084 | Progestogen |
| Norethynodrel | 5(10)-Norethisterone | 0.5 (0.3–0.7) | <0.1–0.22 | 14 | 53 | Progestogen |
| Tibolone | 7α-Methylnorethynodrel | 0.5 (0.45–2.0) | 0.2–0.076 | ? | ? | Progestogen |
| Δ4-Tibolone | 7α-Methylnorethisterone | 0.069–<0.1 | 0.027–<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. | ||||||
| Estrogen | ER RBA (%) | Uterine weight (%) | Uterotrophy | LH levels (%) | SHBG RBA (%) |
|---|---|---|---|---|---|
| Control | – | 100 | – | 100 | – |
| Estradiol (E2) | 100 | 506 ± 20 | +++ | 12–19 | 100 |
| Estrone (E1) | 11 ± 8 | 490 ± 22 | +++ | ? | 20 |
| Estriol (E3) | 10 ± 4 | 468 ± 30 | +++ | 8–18 | 3 |
| Estetrol (E4) | 0.5 ± 0.2 | ? | Inactive | ? | 1 |
| 17α-Estradiol | 4.2 ± 0.8 | ? | ? | ? | ? |
| 2-Hydroxyestradiol | 24 ± 7 | 285 ± 8 | +b | 31–61 | 28 |
| 2-Methoxyestradiol | 0.05 ± 0.04 | 101 | Inactive | ? | 130 |
| 4-Hydroxyestradiol | 45 ± 12 | ? | ? | ? | ? |
| 4-Methoxyestradiol | 1.3 ± 0.2 | 260 | ++ | ? | 9 |
| 4-Fluoroestradiola | 180 ± 43 | ? | +++ | ? | ? |
| 2-Hydroxyestrone | 1.9 ± 0.8 | 130 ± 9 | Inactive | 110–142 | 8 |
| 2-Methoxyestrone | 0.01 ± 0.00 | 103 ± 7 | Inactive | 95–100 | 120 |
| 4-Hydroxyestrone | 11 ± 4 | 351 | ++ | 21–50 | 35 |
| 4-Methoxyestrone | 0.13 ± 0.04 | 338 | ++ | 65–92 | 12 |
| 16α-Hydroxyestrone | 2.8 ± 1.0 | 552 ± 42 | +++ | 7–24 | <0.5 |
| 2-Hydroxyestriol | 0.9 ± 0.3 | 302 | +b | ? | ? |
| 2-Methoxyestriol | 0.01 ± 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. | |||||
- ^ a b c d e f g h H.J. Buchsbaum (6 December 2012). The Menopause. Springer Science & Business Media. pp. 65–. ISBN 978-1-4612-5525-3.
- ^ a b c d Shufeng Zhou (6 April 2016). Cytochrome P450 2D6: Structure, Function, Regulation and Polymorphism. CRC Press. pp. 241–242. ISBN 978-1-4665-9788-4.
- ^ Fotsis T, Järvenpää P, Adlercreutz H (1980). "Identification of 4-hydroxyestriol in pregnancy urine". J. Clin. Endocrinol. Metab. 51 (1): 148–51. doi:10.1210/jcem-51-1-148. PMID 6892918.