:2-Hydroxyestrone

{{Chembox

| ImageFile = 2-Hydroxyestrone.svg

| ImageSize = 200px

| ImageAlt =

| IUPACName = 2,3-Dihydroxyestra-1,3,5(10)-trien-17-one

| SystematicName = (3aS,3bR,9bS,11aS)-7,8-Dihydroxy-11a-methyl-2,3,3a,3b,4,5,9b,10,11,11a-decahydro-1H-cyclopenta[a]phenanthren-1-one

| OtherNames = 2-OHE1; Estra-1,3,5(10)-trien-2,3-diol-17-one

| Section1 = {{Chembox Identifiers

| CASNo = 362-06-1

| ChEBI = 1156

| ChEMBL = 1627343

| KEGG = C05298

| PubChem = 440623

| ChemSpiderID = 389514

| SMILES = C[C@]12CC[C@H]3[C@H]([C@@H]1CCC2=O)CCC4=CC(=C(C=C34)O)O

| StdInChI = 1S/C18H22O3/c1-18-7-6-11-12(14(18)4-5-17(18)21)3-2-10-8-15(19)16(20)9-13(10)11/h8-9,11-12,14,19-20H,2-7H2,1H3/t11-,12+,14-,18-/m0/s1

| StdInChIKey = SWINWPBPEKHUOD-JPVZDGGYSA-N

| UNII = UQS3A06ILY

}}

| Section2 = {{Chembox Properties

| C=18 | H=22 | O=3

| MolarMass = 286.371 g/mol

| Appearance =

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| Section3 = {{Chembox Hazards

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2-Hydroxyestrone (2-OHE1), also known as estra-1,3,5(10)-trien-2,3-diol-17-one, is an endogenous, naturally occurring catechol estrogen and a major metabolite of estrone and estradiol.{{cite book| first1 = Michael | last1 = Oettel | first2 = Ekkehard | last2 = Schillinger | name-list-style = vanc |title=Estrogens and Antiestrogens I: Physiology and Mechanisms of Action of Estrogens and Antiestrogens|url=https://books.google.com/books?id=0BfrCAAAQBAJ&pg=PA235|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-3-642-58616-3|pages=227}}{{cite book|first = David | last = Rakel | name-list-style = vanc |title=Integrative Medicine|url=https://books.google.com/books?id=jlVtJzBwAcEC&pg=PA338|year=2012|publisher=Elsevier Health Sciences|isbn=978-1-4377-1793-8|pages=338–}}{{cite book| vauthors = Buchsbaum HJ |title=The Menopause|url=https://books.google.com/books?id=z0LuBwAAQBAJ&pg=PA65|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-1-4612-5525-3|pages=64–65}} It is formed irreversibly from estrone in the liver and to a lesser extent in other tissues via 2-hydroxylation mediated by cytochrome P450 enzymes, mainly the CYP3A and CYP1A subfamilies. 2-OHE1 is the most abundant catechol estrogen in the body.

2-Hydroxyestrone is not significantly uterotrophic in bioassays, whereas other hydroxylated estrogen metabolites including 2-hydroxyestradiol, 16α-hydroxyestrone, estriol (16α-hydroxyestradiol), 4-hydroxyestradiol, and 4-hydroxyestrone all are.{{cite journal | vauthors = Bhavnani BR, Nisker JA, Martin J, Aletebi F, Watson L, Milne JK | title = Comparison of pharmacokinetics of a conjugated equine estrogen preparation (premarin) and a synthetic mixture of estrogens (C.E.S.) in postmenopausal women | journal = Journal of the Society for Gynecologic Investigation | volume = 7 | issue = 3 | pages = 175–83 | year = 2000 | pmid = 10865186 | doi = 10.1016/s1071-5576(00)00049-6}} In addition, although not antiestrogenic in the uterus,{{cite journal | vauthors = Martucci C, Fishman J | title = Direction of estradiol metabolism as a control of its hormonal action--uterotrophic activity of estradiol metabolites | journal = Endocrinology | volume = 101 | issue = 6 | pages = 1709–15 | date = December 1977 | pmid = 590186 | doi = 10.1210/endo-101-6-1709 | doi-access = free }}{{cite journal | vauthors = Kono S, Brandon DD, Merriam GR, Loriaux DL, Lipsett MB | title = Metabolic clearance rate and uterotropic activity of 2-hydroxyestrone in rats | journal = Endocrinology | volume = 108 | issue = 1 | pages = 40–3 | date = January 1981 | pmid = 7460827 | doi = 10.1210/endo-108-1-40 }} 2-hydroxyestrone shows antiestrogenic effects on luteinizing hormone and prolactin levels.{{cite journal | vauthors = Martucci CP, Fishman J | title = Impact of continuously administered catechol estrogens on uterine growth and luteinizing hormone secretion | journal = Endocrinology | volume = 105 | issue = 6 | pages = 1288–92 | date = December 1979 | pmid = 499073 | doi = 10.1210/endo-105-6-1288 }}{{cite journal | vauthors = Katayama S, Fishman J | title = 2-Hydroxyestrone suppresses and 2-methoxyestrone augments the preovulatory prolactin surge in the cycling rat | journal = Endocrinology | volume = 110 | issue = 4 | pages = 1448–50 | date = April 1982 | pmid = 7199421 | doi = 10.1210/endo-110-4-1448 | doi-access = free }}{{cite journal | vauthors = Okatani Y, Fishman J | title = Suppression of the preovulatory luteinizing hormone surge in the rat by 2-hydroxyestrone: relationship to endogenous estradiol levels | journal = Endocrinology | volume = 115 | issue = 3 | pages = 1082–9 | date = September 1984 | pmid = 6378602 | doi = 10.1210/endo-115-3-1082 }}{{cite journal | vauthors = Okatani Y, Fishman J | title = Inhibition of the preovulatory prolactin surge in the rat by catechol estrogens: functional and temporal specificity | journal = Endocrinology | volume = 119 | issue = 1 | pages = 261–7 | date = July 1986 | pmid = 3013588 | doi = 10.1210/endo-119-1-261 }} The lack of estrogenic or antiestrogenic activity of 2-hydroxyestrone in the uterus may be attributable to an extremely high metabolic clearance rate.{{cite journal | vauthors = MacLusky NJ, Naftolin F, Krey LC, Franks S | title = The catechol estrogens | journal = J. Steroid Biochem. | volume = 15 | pages = 111–24 | date = December 1981 | pmid = 6279963 | doi = 10.1016/0022-4731(81)90265-x }} When incubated at very high concentrations or in combination with a catechol O-methyltransferase (COMT) inhibitor to prevent its metabolism, 2-hydroxyestrone shows antiestrogenic effects in estrogen receptor-positive human breast cancer cells.{{cite journal|last1=Gupta|first1=Mona|last2=McDougal|first2=Andrew|last3=Safe|first3=Stephen|title=Estrogenic and antiestrogenic activities of 16α- and 2-hydroxy metabolites of 17β-estradiol in MCF-7 and T47D human breast cancer cells|journal=The Journal of Steroid Biochemistry and Molecular Biology|volume=67|issue=5–6|year=1998|pages=413–419|issn=0960-0760|doi=10.1016/S0960-0760(98)00135-6|pmid=10030690 |s2cid=54268416 }}{{cite journal | vauthors = Schneider J, Huh MM, Bradlow HL, Fishman J | title = Antiestrogen action of 2-hydroxyestrone on MCF-7 human breast cancer cells | journal = J. Biol. Chem. | volume = 259 | issue = 8 | pages = 4840–5 | date = April 1984 | doi = 10.1016/S0021-9258(17)42922-X | pmid = 6325410 | doi-access = free }}

2-Hydroxyestrone dissociates from the estrogen receptors much more rapidly than does estradiol.{{cite journal | vauthors = Barnea ER, MacLusky NJ, Naftolin F | title = Kinetics of catechol estrogen-estrogen receptor dissociation: a possible factor underlying differences in catechol estrogen biological activity | journal = Steroids | volume = 41 | issue = 5 | pages = 643–56 | date = May 1983 | pmid = 6658896 | doi = 10.1016/0039-128x(83)90030-2 | s2cid = 27048999 }}

{{Selected biological properties of endogenous estrogens in rats}}