16α-Hydroxyestrone

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| ImageFile = 16α-Hydroxyestrone.svg

| ImageSize = 250

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| IUPACName = 3,16α-Dihydroxyestra-1,3,5(10)-trien-17-one

| SystematicName = (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

| OtherNames = Hydroxyestrone; 16-Hydroxyestrone

| Section1 = {{Chembox Identifiers

| CASNo = 566-76-7

| CASNo_Ref = {{cascite|correct|CAS}}

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = JY611949JU

| ChemSpiderID = 103012

| ChEBI = 776

| InChI = 1S/C18H22O3/c1-18-7-6-13-12-5-3-11(19)8-10(12)2-4-14(13)15(18)9-16(20)17(18)21/h3,5,8,13-16,19-20H,2,4,6-7,9H2,1H3/t13-,14-,15+,16-,18+/m1/s1

| PubChem = 115116

| SMILES = C[C@]12CC[C@H]3[C@H]([C@@H]1C[C@H](C2=O)O)CCC4=C3C=CC(=C4)O

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| Section2 = {{Chembox Properties

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

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| Section3 = {{Chembox Hazards

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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.{{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=338–339}}{{cite book|title=Vitamins and Hormones|url=https://books.google.com/books?id=DUst5mwBfN0C&pg=PA282|date=7 September 2005|publisher=Academic Press|isbn=978-0-08-045978-3|pages=282–}} 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.

In terms of relative binding affinity (RBA) for the rat uterine estrogen receptor, 16α-hydroxyestrone showed 2.8% of the affinity of estradiol.{{cite journal | vauthors = Fishman J, Martucci C | title = Biological properties of 16 alpha-hydroxyestrone: implications in estrogen physiology and pathophysiology | journal = J. Clin. Endocrinol. Metab. | volume = 51 | issue = 3 | pages = 611–5 | date = September 1980 | pmid = 7190977 | doi = 10.1210/jcem-51-3-611 }} For comparison, estrone had 11% of the affinity and estriol had 10% of the affinity of estradiol. In contrast to other estrogens, the binding of 16α-hydroxyestrone to the estrogen receptor is reported to be covalent and irreversible.{{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=PA252|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-3-642-58616-3|pages=252–}}{{cite journal | vauthors = Swaneck GE, Fishman J | title = Covalent binding of the endogenous estrogen 16 alpha-hydroxyestrone to estradiol receptor in human breast cancer cells: characterization and intranuclear localization | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 85 | issue = 21 | pages = 7831–5 | date = November 1988 | pmid = 3186693 | pmc = 282290 | doi = 10.1073/pnas.85.21.7831 | bibcode = 1988PNAS...85.7831S | doi-access = free }}{{cite journal | vauthors = Zhu BT, Conney AH | title = Functional role of estrogen metabolism in target cells: review and perspectives | journal = Carcinogenesis | volume = 19 | issue = 1 | pages = 1–27 | date = January 1998 | pmid = 9472688 | doi = 10.1093/carcin/19.1.1 | doi-access = free }}{{cite journal | vauthors = Kuhl H | title = Pharmacology of estrogens and progestogens: influence of different routes of administration | journal = Climacteric | volume = 8 | pages = 3–63 | year = 2005 | issue = Suppl 1 | pmid = 16112947 | doi = 10.1080/13697130500148875 | s2cid = 24616324 | url = http://hormonebalance.org/images/documents/Kuhl%2005%20%20Pharm%20Estro%20Progest%20Climacteric_1313155660.pdf}} 16α-Hydroxyestrone has been reported to have 25% of the vaginal estrogenic potency of estradiol.{{cite journal | vauthors = Fishman J, Martucci C | title = Biological properties of 16 alpha-hydroxyestrone: implications in estrogen physiology and pathophysiology | journal = J. Clin. Endocrinol. Metab. | volume = 51 | issue = 3 | pages = 611–5 | date = September 1980 | pmid = 7190977 | doi = 10.1210/jcem-51-3-611 }} 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.{{cite book|last1=Velardo|first1=Joseph Thomas|title=Hormonal Steroids Biochemistry, Pharmacology, and Therapeutics|chapter=The Actions of Steroid Hormones on Estradiol-17β in Uterine Growth and Enzymorphology|year=1964|pages=463–490|doi=10.1016/B978-0-12-395506-7.50065-0|isbn=9780123955067}} However, 16α-hydroxyestrone was much less potent than estradiol or estrone.

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.{{cite book|title=Index Nominum 2000: International Drug Directory|url=https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA1250|date=January 2000|publisher=Taylor & Francis|isbn=978-3-88763-075-1|pages=1250–}}{{cite book| first1 = Niels F | last1 = Muller | first2 = Rudolf P | last2 = Dessing | author3 = European Society of Clinical Pharmacy | name-list-style = vanc |title=European Drug Index: European Drug Registrations | edition = Fourth|url=https://books.google.com/books?id=2HBPHmclMWIC&pg=PA289|date=19 June 1998|publisher=CRC Press|isbn=978-3-7692-2114-5|pages=289–}}

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