16α-Hydroxyestrone
Chemical compound
From Wikipedia, the free encyclopedia
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.[1][2] 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.[1] Conversely, 16α-hydroxyestrone may help to protect against osteoporosis.[1]
| Names | |
|---|---|
| IUPAC name
3,16α-Dihydroxyestra-1,3,5(10)-trien-17-one | |
| Systematic IUPAC name
(2R,3aS,3bR,9bS,11aS)-2,7-Dihydroxy-11a-methyl-2,3,3a,3b,4,5,9b,10,11,11a-decahydro-1H-cyclopenta[a]phenanthren-1-one | |
| Other names
Hydroxyestrone; 16-Hydroxyestrone | |
| Identifiers | |
3D model (JSmol) |
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| ChEBI | |
| ChemSpider | |
| ECHA InfoCard | 100.164.941 |
PubChem CID |
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| UNII | |
CompTox Dashboard (EPA) |
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| Properties | |
| C18H22O3 | |
| Molar mass | 286.371 g·molâ1 |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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In terms of relative binding affinity (RBA) for the rat uterine estrogen receptor, 16α-hydroxyestrone showed 2.8% of the affinity of estradiol.[3] For comparison, estrone had 11% of the affinity and estriol had 10% of the affinity of estradiol.[3] In contrast to other estrogens, the binding of 16α-hydroxyestrone to the estrogen receptor is reported to be covalent and irreversible.[4][5][6][7] 16α-Hydroxyestrone has been reported to have 25% of the vaginal estrogenic potency of estradiol.[3] The maximal uterotrophic and antigonadotropic effect of 16α-hydroxyestrone was equivalent to those of estradiol and estriol, indicating that 16α-hydroxyestrone is a fully effective estrogen.[3][8] However, 16α-hydroxyestrone was much less potent than estradiol or estrone.[8]
The C3 and C16α diacetate ester of 16α-hydroxyestrone, hydroxyestrone diacetate (brand names Colpoginon, Colpormon, Hormobion, and Hormocervix), has been marketed and used medically as an estrogen in Europe.[9][10]
| Estrogen | ER RBA (%) | Uterine weight (%) | Uterotrophy | LH levels (%) | SHBG RBA (%) |
|---|---|---|---|---|---|
| Control | â | 100 | â | 100 | â |
| Estradiol (E2) | 100 | 506 ± 20 | +++ | 12â19 | 100 |
| Estrone (E1) | 11 ± 8 | 490 ± 22 | +++ | ? | 20 |
| Estriol (E3) | 10 ± 4 | 468 ± 30 | +++ | 8â18 | 3 |
| Estetrol (E4) | 0.5 ± 0.2 | ? | Inactive | ? | 1 |
| 17α-Estradiol | 4.2 ± 0.8 | ? | ? | ? | ? |
| 2-Hydroxyestradiol | 24 ± 7 | 285 ± 8 | +b | 31â61 | 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 | 110â142 | 8 |
| 2-Methoxyestrone | 0.01 ± 0.00 | 103 ± 7 | Inactive | 95â100 | 120 |
| 4-Hydroxyestrone | 11 ± 4 | 351 | ++ | 21â50 | 35 |
| 4-Methoxyestrone | 0.13 ± 0.04 | 338 | ++ | 65â92 | 12 |
| 16α-Hydroxyestrone | 2.8 ± 1.0 | 552 ± 42 | +++ | 7â24 | <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: [11][12][13][14][15][16][17][18][19] | |||||
