2-Hydroxyestrone

Last updated
2-Hydroxyestrone
2-Hydroxyestrone.svg
Names
IUPAC name
2,3-Dihydroxyestra-1,3,5(10)-trien-17-one
Systematic IUPAC name
(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
Other names
2-OHE1; Estra-1,3,5(10)-trien-2,3-diol-17-one
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.164.607 OOjs UI icon edit-ltr-progressive.svg
KEGG
PubChem CID
UNII
  • InChI=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
    Key: SWINWPBPEKHUOD-JPVZDGGYSA-N
  • C[C@]12CC[C@H]3[C@H]([C@@H]1CCC2=O)CCC4=CC(=C(C=C34)O)O
Properties
C18H22O3
Molar mass 286.371 g/mol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

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. [1] [2] [3] 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. [1] [3] 2-OHE1 is the most abundant catechol estrogen in the body. [3]

Contents

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. [1] [4] In addition, although not antiestrogenic in the uterus, [5] [6] 2-hydroxyestrone shows antiestrogenic effects on luteinizing hormone and prolactin levels. [7] [8] [9] [10] The lack of estrogenic or antiestrogenic activity of 2-hydroxyestrone in the uterus may be attributable to an extremely high metabolic clearance rate. [6] [11] 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. [12] [13]

2-Hydroxyestrone dissociates from the estrogen receptors much more rapidly than does estradiol. [14]

Selected biological properties of endogenous estrogens in rats
Estrogen ER Tooltip Estrogen receptor RBA Tooltip relative binding affinity (%) Uterine weight (%) Uterotrophy LH Tooltip Luteinizing hormone levels (%) SHBG Tooltip Sex hormone-binding globulin RBA Tooltip relative binding affinity (%)
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-Estradiol 4.2 ± 0.8 ? ? ? ?
2-Hydroxyestradiol 24 ± 7285 ± 8+b31–6128
2-Methoxyestradiol 0.05 ± 0.04101Inactive ?130
4-Hydroxyestradiol 45 ± 12 ? ? ? ?
4-Methoxyestradiol 1.3 ± 0.2260++ ?9
4-Fluoroestradiol a180 ± 43 ?+++ ? ?
2-Hydroxyestrone1.9 ± 0.8130 ± 9Inactive110–1428
2-Methoxyestrone 0.01 ± 0.00103 ± 7Inactive95–100120
4-Hydroxyestrone 11 ± 4351++21–5035
4-Methoxyestrone 0.13 ± 0.04338++65–9212
16α-Hydroxyestrone 2.8 ± 1.0552 ± 42+++7–24<0.5
2-Hydroxyestriol 0.9 ± 0.3302+b ? ?
2-Methoxyestriol 0.01 ± 0.00 ?Inactive ?4
Notes: Values are mean ± SD or range. ERRBA = 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.

See also

Related Research Articles

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Estriol (E3), also spelled oestriol, is a steroid, a weak estrogen, and a minor female sex hormone. It is one of three major endogenous estrogens, the others being estradiol and estrone. Levels of estriol in women who are not pregnant are almost undetectable. However, during pregnancy, estriol is synthesized in very high quantities by the placenta and is the most produced estrogen in the body by far, although circulating levels of estriol are similar to those of other estrogens due to a relatively high rate of metabolism and excretion. Relative to estradiol, both estriol and estrone have far weaker activity as estrogens.

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<span class="mw-page-title-main">Estrone sulfate</span> Chemical compound

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<span class="mw-page-title-main">Broparestrol</span> Chemical compound

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<span class="mw-page-title-main">Estradiol sulfate</span> Chemical compound

Estradiol sulfate (E2S), or 17β-estradiol 3-sulfate, is a natural, endogenous steroid and an estrogen ester. E2S itself is biologically inactive, but it can be converted by steroid sulfatase into estradiol, which is a potent estrogen. Simultaneously, estrogen sulfotransferases convert estradiol to E2S, resulting in an equilibrium between the two steroids in various tissues. Estrone and E2S are the two immediate metabolic sources of estradiol. E2S can also be metabolized into estrone sulfate (E1S), which in turn can be converted into estrone and estradiol. Circulating concentrations of E2S are much lower than those of E1S. High concentrations of E2S are present in breast tissue, and E2S has been implicated in the biology of breast cancer via serving as an active reservoir of estradiol.

<span class="mw-page-title-main">8,9-Dehydroestrone</span> Chemical compound

8,9-Dehydroestrone, or Δ8-estrone, also known as estra-1,3,5(10),8-tetraen-3-ol-17-one, is a naturally occurring estrogen found in horses which is closely related to equilin, equilenin, and estrone, and, as the 3-sulfate ester sodium salt, is a minor constituent (3.5%) of conjugated estrogens (Premarin). It produces 8,9-dehydro-17β-estradiol as an important active metabolite, analogously to conversion of estrone or estrone sulfate into estradiol. The compound was first described in 1997. In addition to 8,9-dehydroestrone and 8,9-dehydro-17β-estradiol, 8,9-dehydro-17α-estradiol is likely also to be present in conjugated estrogens, but has not been identified at this time.

<span class="mw-page-title-main">2-Hydroxyestradiol</span> Chemical compound

2-Hydroxyestradiol (2-OHE2), also known as estra-1,3,5(10)-triene-2,3,17β-triol, is an endogenous steroid, catechol estrogen, and metabolite of estradiol, as well as a positional isomer of estriol.

<span class="mw-page-title-main">16α-Hydroxyestrone</span> Chemical compound

16α-Hydroxyestrone (16α-OH-E1), or hydroxyestrone, also known as estra-1,3,5(10)-triene-3,16α-diol-17-one, is an endogenous steroidal estrogen and a major metabolite of estrone, as well as an intermediate in the biosynthesis of estriol. It is a potent estrogen similarly to estrone, and it has been suggested that the ratio of 16α-hydroxyestrone to 2-hydroxyestrone, the latter being much less estrogenic in comparison and even antiestrogenic in the presence of more potent estrogens like estradiol, may be involved in the pathophysiology of breast cancer. Conversely, 16α-hydroxyestrone may help to protect against osteoporosis.

<span class="mw-page-title-main">Catechol estrogen</span>

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:

<span class="mw-page-title-main">Estrone glucuronide</span> Chemical compound

Estrone glucuronide, or estrone-3-D-glucuronide, is a conjugated metabolite of estrone. It is formed from estrone in the liver by UDP-glucuronyltransferase via attachment of glucuronic acid and is eventually excreted in the urine by the kidneys. It has much higher water solubility than does estrone. Glucuronides are the most abundant estrogen conjugates and estrone glucuronide is the dominant metabolite of estradiol.

<span class="mw-page-title-main">4-Hydroxyestradiol</span> Chemical compound

4-Hydroxyestradiol (4-OHE2), also known as estra-1,3,5(10)-triene-3,4,17β-triol, is an endogenous, naturally occurring catechol estrogen and a minor metabolite of estradiol. It is estrogenic, similarly to many other hydroxylated estrogen metabolites such as 2-hydroxyestradiol, 16α-hydroxyestrone, estriol (16α-hydroxyestradiol), and 4-hydroxyestrone but unlike 2-hydroxyestrone.

<span class="mw-page-title-main">4-Hydroxyestrone</span> Chemical compound

4-Hydroxyestrone (4-OHE1), also known as estra-1,3,5(10)-triene-3,4-diol-17-one, is an endogenous, naturally occurring catechol estrogen, neuroestrogen and a minor metabolite of estrone and estradiol. It is estrogenic, similarly to many other hydroxylated estrogen metabolites such as 2-hydroxyestradiol, 16α-hydroxyestrone, estriol (16α-hydroxyestradiol), and 4-hydroxyestradiol but unlike 2-hydroxyestrone. 4-OHE1 is also categorized as a carcinogen.

<span class="mw-page-title-main">4-Methoxyestradiol</span> Chemical compound

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<span class="mw-page-title-main">Hydroxylation of estradiol</span>

The hydroxylation of estradiol is one of the major routes of metabolism of the estrogen steroid hormone estradiol. It is hydroxylated into the catechol estrogens 2-hydroxyestradiol and 4-hydroxyestradiol and into estriol (16α-hydroxyestradiol), reactions which are catalyzed by cytochrome P450 enzymes predominantly in the liver, but also in various other tissues.

<span class="mw-page-title-main">Estriol 3-glucuronide</span> Chemical compound

Estriol 3-glucuronide, or oestriol 3-glucuronide, also known as estriol 3-β-D-glucosiduronic acid, is a natural, steroidal estrogen and a glucuronic acid conjugate of estriol. It is found in the urine of women as a reversibly formed metabolite of estriol. The positional isomer of estriol 3-glucuronide, estriol 16α-glucuronide, also occurs as an endogenous metabolite of estriol, but to a much greater extent in comparison.

<span class="mw-page-title-main">RU-16117</span> Chemical compound

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<span class="mw-page-title-main">Estrone sulfate (medication)</span> Chemical compound

Estrone sulfate (E1S) is an estrogen medication and naturally occurring steroid hormone. It is used in menopausal hormone therapy among other indications. As the sodium salt, it is the major estrogen component of conjugated estrogens (Premarin) and esterified estrogens. In addition, E1S is used on its own as the piperazine salt estropipate. The compound also occurs as a major and important metabolite of estradiol and estrone. E1S is most commonly taken by mouth, but in the form of Premarin can also be taken by parenteral routes such as transdermal, vaginal, and injection.

<span class="mw-page-title-main">16β-Hydroxyestrone</span> Chemical compound

16β-Hydroxyestrone (16β-OH-E1) is an endogenous estrogen which serves as a metabolite of estrone as well as a metabolic intermediate in the transformation of estrone into epiestriol (16β-hydroxyestradiol). 16β-Hydroxyestrone has similar estrogenic activity to that of 16α-hydroxyestrone. It is less potent than estradiol or estrone but can produce similar maximal uterotrophy at sufficiently high doses, suggesting a fully estrogenic profile.

<span class="mw-page-title-main">16-Ketoestrone</span> Chemical compound

16-Ketoestrone is an endogenous estrogen related to 16α-hydroxyestrone and 16β-hydroxyestrone. In contrast to 16α-hydroxyestrone and 16β-hydroxyestrone, but similarly to 16-ketoestradiol, 16-ketoestrone is a very weak estrogen with less than 1/1000 the estrogenic potency of estrone in the uterus. 16-Ketoestrone has been reported to act as an inhibitor of 17β-hydroxysteroid dehydrogenases. 16-Ketoestrone can be converted by 16α-hydroxysteroid dehydrogenase into estriol in the body.

<span class="mw-page-title-main">Estrogen provocation test</span> Medical diagnostic method

The estrogen provocation test, also known as the estrogen stimulation test or estrogen challenge test, is a diagnostic procedure used to evaluate the function of the hypothalamic–pituitary–gonadal axis. It involves the administration of a large amount of estrogen, resulting in estrogenic exposure similar to or greater than normal preovulatory estradiol levels, in an attempt to induce a positive feedback surge in levels of the gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Estrogens that have been used in the estrogen provocation test include estradiol benzoate, estradiol valerate, ethinylestradiol, and high-dose transdermal estradiol patches. The test involves sustained estrogenic exposure equivalent to estradiol levels of 200 to 300 pg/mL or more for at least 50 hours and results in a surge in gonadotropin levels about 32 to 72 hours following initiation of estrogenic exposure. Levels of LH and FSH increase during the gonadotropin surge by about 10-fold and 4-fold, respectively.

References

  1. 1 2 3 Oettel M, Schillinger E (6 December 2012). Estrogens and Antiestrogens I: Physiology and Mechanisms of Action of Estrogens and Antiestrogens. Springer Science & Business Media. p. 227. ISBN   978-3-642-58616-3.
  2. ↑ Rakel D (2012). Integrative Medicine. Elsevier Health Sciences. pp. 338–. ISBN   978-1-4377-1793-8.
  3. 1 2 3 Buchsbaum HJ (6 December 2012). The Menopause. Springer Science & Business Media. pp. 64–65. ISBN   978-1-4612-5525-3.
  4. ↑ Bhavnani BR, Nisker JA, Martin J, Aletebi F, Watson L, Milne JK (2000). "Comparison of pharmacokinetics of a conjugated equine estrogen preparation (premarin) and a synthetic mixture of estrogens (C.E.S.) in postmenopausal women". Journal of the Society for Gynecologic Investigation. 7 (3): 175–83. doi:10.1016/s1071-5576(00)00049-6. PMID   10865186.
  5. ↑ Martucci C, Fishman J (December 1977). "Direction of estradiol metabolism as a control of its hormonal action--uterotrophic activity of estradiol metabolites". Endocrinology. 101 (6): 1709–15. doi: 10.1210/endo-101-6-1709 . PMID   590186.
  6. 1 2 Kono S, Brandon DD, Merriam GR, Loriaux DL, Lipsett MB (January 1981). "Metabolic clearance rate and uterotropic activity of 2-hydroxyestrone in rats". Endocrinology. 108 (1): 40–3. doi:10.1210/endo-108-1-40. PMID   7460827.
  7. ↑ Martucci CP, Fishman J (December 1979). "Impact of continuously administered catechol estrogens on uterine growth and luteinizing hormone secretion". Endocrinology. 105 (6): 1288–92. doi:10.1210/endo-105-6-1288. PMID   499073.
  8. ↑ Katayama S, Fishman J (April 1982). "2-Hydroxyestrone suppresses and 2-methoxyestrone augments the preovulatory prolactin surge in the cycling rat". Endocrinology. 110 (4): 1448–50. doi: 10.1210/endo-110-4-1448 . PMID   7199421.
  9. ↑ Okatani Y, Fishman J (September 1984). "Suppression of the preovulatory luteinizing hormone surge in the rat by 2-hydroxyestrone: relationship to endogenous estradiol levels". Endocrinology. 115 (3): 1082–9. doi:10.1210/endo-115-3-1082. PMID   6378602.
  10. ↑ Okatani Y, Fishman J (July 1986). "Inhibition of the preovulatory prolactin surge in the rat by catechol estrogens: functional and temporal specificity". Endocrinology. 119 (1): 261–7. doi:10.1210/endo-119-1-261. PMID   3013588.
  11. ↑ MacLusky NJ, Naftolin F, Krey LC, Franks S (December 1981). "The catechol estrogens". J. Steroid Biochem. 15: 111–24. doi:10.1016/0022-4731(81)90265-x. PMID   6279963.
  12. ↑ Gupta, Mona; McDougal, Andrew; Safe, Stephen (1998). "Estrogenic and antiestrogenic activities of 16α- and 2-hydroxy metabolites of 17β-estradiol in MCF-7 and T47D human breast cancer cells". The Journal of Steroid Biochemistry and Molecular Biology. 67 (5–6): 413–419. doi:10.1016/S0960-0760(98)00135-6. ISSN   0960-0760. PMID   10030690. S2CID   54268416.
  13. ↑ Schneider J, Huh MM, Bradlow HL, Fishman J (April 1984). "Antiestrogen action of 2-hydroxyestrone on MCF-7 human breast cancer cells". J. Biol. Chem. 259 (8): 4840–5. doi: 10.1016/S0021-9258(17)42922-X . PMID   6325410.
  14. ↑ Barnea ER, MacLusky NJ, Naftolin F (May 1983). "Kinetics of catechol estrogen-estrogen receptor dissociation: a possible factor underlying differences in catechol estrogen biological activity". Steroids. 41 (5): 643–56. doi:10.1016/0039-128x(83)90030-2. PMID   6658896. S2CID   27048999.
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