16α-Hydroxyestrone

16α-Hydroxyestrone
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
CAS Number	566-76-7 ;
3D model (JSmol)	Interactive image;
ChEBI	CHEBI:776;
ChemSpider	103012;
ECHA InfoCard	100.164.941
PubChem CID	115116;
UNII	JY611949JU ;
CompTox Dashboard (EPA)	DTXSID901047947 ;
	InChI 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;
	SMILES C[C@]12CC[C@H]3[C@H]([C@@H]1C[C@H](C2=O)O)CCC4=C3C=CC(=C4)O;
Properties
Chemical formula	C18H22O3
Molar mass	286.371 g·mol−1
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references

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]

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]

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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-Fluoroestradiol^a	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.