2-Methoxyestriol

Not to be confused with 2-Methoxyestradiol.
2-Methoxyestriol
Names
IUPAC name
2-Methoxyestra-1,3,5(10)-triene-3,16α,17β-triol
Systematic IUPAC name
(1R,2R,3aS,3bR,9bS,11aS)-8-Methoxy-11a-methyl-2,3,3a,3b,4,5,9b,10,11,11a-decahydro-1H-cyclopenta[a]phenanthrene-1,2,7-triol
Other names
2-MeO-E3
Identifiers
3D model (JSmol)
ChEMBL
ChemSpider
  • InChI=1S/C19H26O4/c1-19-6-5-11-12(14(19)9-16(21)18(19)22)4-3-10-7-15(20)17(23-2)8-13(10)11/h7-8,11-12,14,16,18,20-22H,3-6,9H2,1-2H3/t11-,12+,14-,16+,18-,19-/m0/s1
    Key: PEXPJFWTSZLEAQ-YSYMNNNUSA-N
  • C[C@]12CC[C@H]3[C@H]([C@@H]1C[C@H]([C@@H]2O)O)CCC4=CC(=C(C=C34)OC)O
Properties
C19H26O4
Molar mass 318.413 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

2-Methoxyestriol (2-MeO-E3) is an endogenous estrogen metabolite.[1][2][3] It is specifically a metabolite of estriol and 2-hydroxyestriol.[1][2][3] It has negligible affinity for the estrogen receptors and no estrogenic activity.[4] However, 2-methoxyestriol does have some non-estrogen receptor-mediated cholesterol-lowering effects.[5]

Selected biological properties of endogenous estrogens in rats
Estrogen ERTooltip Estrogen receptor RBATooltip relative binding affinity (%) Uterine weight (%) Uterotrophy LHTooltip Luteinizing hormone levels (%) SHBGTooltip Sex hormone-binding globulin RBATooltip relative binding affinity (%)
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.
  1. ^ a b Fishman J, Gallagher TF (October 1958). "2-Methoxyestriol: a new metabolite of estradiol in man". Arch. Biochem. Biophys. 77 (2): 511–3. doi:10.1016/0003-9861(58)90097-3. PMID 13584013.
  2. ^ a b King RJ (May 1961). "Oestriol metabolism by rat- and rabbit-liver slices. Isolation of 2-methoxyoestriol and 2-hydroxyestriol". Biochem. J. 79 (2): 355–61. doi:10.1042/bj0790355. PMC 1205847. PMID 13756104.
  3. ^ a b Fujii Y, Teranishi M, Nakada K, Yamazaki M, Kishida S, Miyabo S (September 1988). "Radioimmunoassay of 2-methoxyestriol in pregnancy plasma". Horm. Metab. Res. 20 (9): 599–600. doi:10.1055/s-2007-1010895. PMID 3198067. S2CID 260170130.
  4. ^ Martucci CP (July 1983). "The role of 2-methoxyestrone in estrogen action". J. Steroid Biochem. 19 (1B): 635–8. doi:10.1016/0022-4731(83)90229-7. PMID 6310247.
  5. ^ Kono, Shinzo; Higa, Hiroaki; Sunagawa, Hajime (1989). "Hypocholesterolemic Effect of Long-Term Continuous Administration of 2-Methoxyestriol in Dietary Hypercholesterolemic Rats". Journal of Clinical Biochemistry and Nutrition. 6 (1): 49–56. doi:10.3164/jcbn.6.49. ISSN 1880-5086.