Estrone sulfate, the 3-sulfate conjugate of estrone.
Estriol glucuronide, the 16α-glucuronide conjugate of estriol.

An estrogen conjugate is a conjugate of an endogenous estrogen. They occur naturally in the body as metabolites of estrogens and can be reconverted back into estrogens. They serve as a circulating reservoir for estrogen, particularly in the case of orally administered pharmaceutical estradiol. Estrogen conjugates include sulfate and/or glucuronide conjugates of estradiol, estrone, and estriol:

Estrogen conjugates are conjugated at the C3, C16α, and/or C17β positions, where hydroxyl groups are available.[1]

Estrogen conjugates have been used as pharmaceutical estrogens, as in estrone sulfate as estropipate (piperazine estrone sulfate) and in conjugated estrogens (Premarin) and conjugated estriol (Progynon, Emmenin).

Affinities and estrogenic potencies of estrogen esters and ethers at the estrogen receptors
Estrogen Other names RBATooltip Relative binding affinity (%)a REP (%)b
ER ERα ERβ
Estradiol E2 100 100 100
Estradiol 3-sulfate E2S; E2-3S  ? 0.02 0.04
Estradiol 3-glucuronide E2-3G  ? 0.02 0.09
Estradiol 17β-glucuronide E2-17G  ? 0.002 0.0002
Estradiol benzoate EB; Estradiol 3-benzoate 10 1.1 0.52
Estradiol 17β-acetate E2-17A 31–45 24  ?
Estradiol diacetate EDA; Estradiol 3,17β-diacetate  ? 0.79  ?
Estradiol propionate EP; Estradiol 17β-propionate 19–26 2.6  ?
Estradiol valerate EV; Estradiol 17β-valerate 2–11 0.04–21  ?
Estradiol cypionate EC; Estradiol 17β-cypionate  ?c 4.0  ?
Estradiol palmitate Estradiol 17β-palmitate 0  ?  ?
Estradiol stearate Estradiol 17β-stearate 0  ?  ?
Estrone E1; 17-Ketoestradiol 11 5.3–38 14
Estrone sulfate E1S; Estrone 3-sulfate 2 0.004 0.002
Estrone glucuronide E1G; Estrone 3-glucuronide  ? <0.001 0.0006
Ethinylestradiol EE; 17α-Ethynylestradiol 100 17–150 129
Mestranol EE 3-methyl ether 1 1.3–8.2 0.16
Quinestrol EE 3-cyclopentyl ether  ? 0.37  ?
Footnotes: a = Relative binding affinities (RBAs) were determined via in-vitro displacement of labeled estradiol from estrogen receptors (ERs) generally of rodent uterine cytosol. Estrogen esters are variably hydrolyzed into estrogens in these systems (shorter ester chain length -> greater rate of hydrolysis) and the ER RBAs of the esters decrease strongly when hydrolysis is prevented. b = Relative estrogenic potencies (REPs) were calculated from half-maximal effective concentrations (EC50) that were determined via in-vitro β‐galactosidase (β-gal) and green fluorescent protein (GFP) production assays in yeast expressing human ERα and human ERβ. Both mammalian cells and yeast have the capacity to hydrolyze estrogen esters. c = The affinities of estradiol cypionate for the ERs are similar to those of estradiol valerate and estradiol benzoate (figure). Sources: See template page.
Affinities of estrogen receptor ligands for the ERα and ERβ
LigandOther namesRelative binding affinities (RBA, %)aAbsolute binding affinities (Ki, nM)aAction
ERαERβERαERβ
EstradiolE2; 17β-Estradiol1001000.115 (0.04–0.24)0.15 (0.10–2.08)Estrogen
EstroneE1; 17-Ketoestradiol16.39 (0.7–60)6.5 (1.36–52)0.445 (0.3–1.01)1.75 (0.35–9.24)Estrogen
EstriolE3; 16α-OH-17β-E212.65 (4.03–56)26 (14.0–44.6)0.45 (0.35–1.4)0.7 (0.63–0.7)Estrogen
EstetrolE4; 15α,16α-Di-OH-17β-E24.03.04.919Estrogen
Alfatradiol17α-Estradiol20.5 (7–80.1)8.195 (2–42)0.2–0.520.43–1.2Metabolite
16-Epiestriol16β-Hydroxy-17β-estradiol7.795 (4.94–63)50 ? ?Metabolite
17-Epiestriol16α-Hydroxy-17α-estradiol55.45 (29–103)79–80 ? ?Metabolite
16,17-Epiestriol16β-Hydroxy-17α-estradiol1.013 ? ?Metabolite
2-Hydroxyestradiol2-OH-E222 (7–81)11–352.51.3Metabolite
2-Methoxyestradiol2-MeO-E20.0027–2.01.0 ? ?Metabolite
4-Hydroxyestradiol4-OH-E213 (8–70)7–561.01.9Metabolite
4-Methoxyestradiol4-MeO-E22.01.0 ? ?Metabolite
2-Hydroxyestrone2-OH-E12.0–4.00.2–0.4 ? ?Metabolite
2-Methoxyestrone2-MeO-E1<0.001–<1<1 ? ?Metabolite
4-Hydroxyestrone4-OH-E11.0–2.01.0 ? ?Metabolite
4-Methoxyestrone4-MeO-E1<1<1 ? ?Metabolite
16α-Hydroxyestrone16α-OH-E1; 17-Ketoestriol2.0–6.535 ? ?Metabolite
2-Hydroxyestriol2-OH-E32.01.0 ? ?Metabolite
4-Methoxyestriol4-MeO-E31.01.0 ? ?Metabolite
Estradiol sulfateE2S; Estradiol 3-sulfate<1<1 ? ?Metabolite
Estradiol disulfateEstradiol 3,17β-disulfate0.0004 ? ? ?Metabolite
Estradiol 3-glucuronideE2-3G0.0079 ? ? ?Metabolite
Estradiol 17β-glucuronideE2-17G0.0015 ? ? ?Metabolite
Estradiol 3-gluc. 17β-sulfateE2-3G-17S0.0001 ? ? ?Metabolite
Estrone sulfateE1S; Estrone 3-sulfate<1<1>10>10Metabolite
Estradiol benzoateEB; Estradiol 3-benzoate10 ? ? ?Estrogen
Estradiol 17β-benzoateE2-17B11.332.6 ? ?Estrogen
Estrone methyl etherEstrone 3-methyl ether0.145 ? ? ?Estrogen
ent-Estradiol1-Estradiol1.31–12.349.44–80.07 ? ?Estrogen
Equilin7-Dehydroestrone13 (4.0–28.9)13.0–490.790.36Estrogen
Equilenin6,8-Didehydroestrone2.0–157.0–200.640.62Estrogen
17β-Dihydroequilin7-Dehydro-17β-estradiol7.9–1137.9–1080.090.17Estrogen
17α-Dihydroequilin7-Dehydro-17α-estradiol18.6 (18–41)14–320.240.57Estrogen
17β-Dihydroequilenin6,8-Didehydro-17β-estradiol35–6890–1000.150.20Estrogen
17α-Dihydroequilenin6,8-Didehydro-17α-estradiol20490.500.37Estrogen
Δ8-Estradiol8,9-Dehydro-17β-estradiol68720.150.25Estrogen
Δ8-Estrone8,9-Dehydroestrone19320.520.57Estrogen
EthinylestradiolEE; 17α-Ethynyl-17β-E2120.9 (68.8–480)44.4 (2.0–144)0.02–0.050.29–0.81Estrogen
MestranolEE 3-methyl ether ?2.5 ? ?Estrogen
MoxestrolRU-2858; 11β-Methoxy-EE35–435–200.52.6Estrogen
Methylestradiol17α-Methyl-17β-estradiol7044 ? ?Estrogen
DiethylstilbestrolDES; Stilbestrol129.5 (89.1–468)219.63 (61.2–295)0.040.05Estrogen
HexestrolDihydrodiethylstilbestrol153.6 (31–302)60–2340.060.06Estrogen
DienestrolDehydrostilbestrol37 (20.4–223)56–4040.050.03Estrogen
Benzestrol (B2)–114 ? ? ?Estrogen
ChlorotrianiseneTACE1.74 ?15.30 ?Estrogen
TriphenylethyleneTPE0.074 ? ? ?Estrogen
TriphenylbromoethyleneTPBE2.69 ? ? ?Estrogen
TamoxifenICI-46,4743 (0.1–47)3.33 (0.28–6)3.4–9.692.5SERM
Afimoxifene4-Hydroxytamoxifen; 4-OHT100.1 (1.7–257)10 (0.98–339)2.3 (0.1–3.61)0.04–4.8SERM
Toremifene4-Chlorotamoxifen; 4-CT ? ?7.14–20.315.4SERM
ClomifeneMRL-4125 (19.2–37.2)120.91.2SERM
CyclofenilF-6066; Sexovid151–152243 ? ?SERM
NafoxidineU-11,000A30.9–44160.30.8SERM
Raloxifene–41.2 (7.8–69)5.34 (0.54–16)0.188–0.5220.2SERM
ArzoxifeneLY-353,381 ? ?0.179 ?SERM
LasofoxifeneCP-336,15610.2–16619.00.229 ?SERM
OrmeloxifeneCentchroman ? ?0.313 ?SERM
Levormeloxifene6720-CDRI; NNC-460,0201.551.88 ? ?SERM
OspemifeneDeaminohydroxytoremifene0.82–2.630.59–1.22 ? ?SERM
Bazedoxifene– ? ?0.053 ?SERM
EtacstilGW-56384.3011.5 ? ?SERM
ICI-164,384–63.5 (3.70–97.7)1660.20.08Antiestrogen
FulvestrantICI-182,78043.5 (9.4–325)21.65 (2.05–40.5)0.421.3Antiestrogen
PropylpyrazoletriolPPT49 (10.0–89.1)0.120.4092.8ERα agonist
16α-LE216α-Lactone-17β-estradiol14.6–570.0890.27131ERα agonist
16α-Iodo-E216α-Iodo-17β-estradiol30.22.30 ? ?ERα agonist
MethylpiperidinopyrazoleMPP110.05 ? ?ERα antagonist
DiarylpropionitrileDPN0.12–0.256.6–1832.41.7ERβ agonist
8β-VE28β-Vinyl-17β-estradiol0.3522.0–8312.90.50ERβ agonist
PrinaberelERB-041; WAY-202,0410.2767–72 ? ?ERβ agonist
ERB-196WAY-202,196 ?180 ? ?ERβ agonist
ErteberelSERBA-1; LY-500,307 ? ?2.680.19ERβ agonist
SERBA-2– ? ?14.51.54ERβ agonist
Coumestrol–9.225 (0.0117–94)64.125 (0.41–185)0.14–80.00.07–27.0Xenoestrogen
Genistein–0.445 (0.0012–16)33.42 (0.86–87)2.6–1260.3–12.8Xenoestrogen
Equol–0.2–0.2870.85 (0.10–2.85) ? ?Xenoestrogen
Daidzein–0.07 (0.0018–9.3)0.7865 (0.04–17.1)2.085.3Xenoestrogen
Biochanin A–0.04 (0.022–0.15)0.6225 (0.010–1.2)1748.9Xenoestrogen
Kaempferol–0.07 (0.029–0.10)2.2 (0.002–3.00) ? ?Xenoestrogen
Naringenin–0.0054 (<0.001–0.01)0.15 (0.11–0.33) ? ?Xenoestrogen
8-Prenylnaringenin8-PN4.4 ? ? ?Xenoestrogen
Quercetin–<0.001–0.010.002–0.040 ? ?Xenoestrogen
Ipriflavone–<0.01<0.01 ? ?Xenoestrogen
Miroestrol–0.39 ? ? ?Xenoestrogen
Deoxymiroestrol–2.0 ? ? ?Xenoestrogen
β-Sitosterol–<0.001–0.0875<0.001–0.016 ? ?Xenoestrogen
Resveratrol–<0.001–0.0032 ? ? ?Xenoestrogen
α-Zearalenol–48 (13–52.5) ? ? ?Xenoestrogen
β-Zearalenol–0.6 (0.032–13) ? ? ?Xenoestrogen
Zeranolα-Zearalanol48–111 ? ? ?Xenoestrogen
Taleranolβ-Zearalanol16 (13–17.8)140.80.9Xenoestrogen
ZearalenoneZEN7.68 (2.04–28)9.45 (2.43–31.5) ? ?Xenoestrogen
ZearalanoneZAN0.51 ? ? ?Xenoestrogen
Bisphenol ABPA0.0315 (0.008–1.0)0.135 (0.002–4.23)19535Xenoestrogen
EndosulfanEDS<0.001–<0.01<0.01 ? ?Xenoestrogen
KeponeChlordecone0.0069–0.2 ? ? ?Xenoestrogen
o,p'-DDT–0.0073–0.4 ? ? ?Xenoestrogen
p,p'-DDT–0.03 ? ? ?Xenoestrogen
Methoxychlorp,p'-Dimethoxy-DDT0.01 (<0.001–0.02)0.01–0.13 ? ?Xenoestrogen
HPTEHydroxychlor; p,p'-OH-DDT1.2–1.7 ? ? ?Xenoestrogen
TestosteroneT; 4-Androstenolone<0.0001–<0.01<0.002–0.040>5000>5000Androgen
DihydrotestosteroneDHT; 5α-Androstanolone0.01 (<0.001–0.05)0.0059–0.17221–>500073–1688Androgen
Nandrolone19-Nortestosterone; 19-NT0.010.2376553Androgen
DehydroepiandrosteroneDHEA; Prasterone0.038 (<0.001–0.04)0.019–0.07245–1053163–515Androgen
5-AndrostenediolA5; Androstenediol6173.60.9Androgen
4-Androstenediol–0.50.62319Androgen
4-AndrostenedioneA4; Androstenedione<0.01<0.01>10000>10000Androgen
3α-Androstanediol3α-Adiol0.070.326048Androgen
3β-Androstanediol3β-Adiol3762Androgen
Androstanedione5α-Androstanedione<0.01<0.01>10000>10000Androgen
Etiocholanedione5β-Androstanedione<0.01<0.01>10000>10000Androgen
Methyltestosterone17α-Methyltestosterone<0.0001 ? ? ?Androgen
Ethinyl-3α-androstanediol17α-Ethynyl-3α-adiol4.0<0.07 ? ?Estrogen
Ethinyl-3β-androstanediol17α-Ethynyl-3β-adiol505.6 ? ?Estrogen
ProgesteroneP4; 4-Pregnenedione<0.001–0.6<0.001–0.010 ? ?Progestogen
NorethisteroneNET; 17α-Ethynyl-19-NT0.085 (0.0015–<0.1)0.1 (0.01–0.3)1521084Progestogen
Norethynodrel5(10)-Norethisterone0.5 (0.3–0.7)<0.1–0.221453Progestogen
Tibolone7α-Methylnorethynodrel0.5 (0.45–2.0)0.2–0.076 ? ?Progestogen
Δ4-Tibolone7α-Methylnorethisterone0.069–<0.10.027–<0.1 ? ?Progestogen
3α-Hydroxytibolone–2.5 (1.06–5.0)0.6–0.8 ? ?Progestogen
3β-Hydroxytibolone–1.6 (0.75–1.9)0.070–0.1 ? ?Progestogen
Footnotes: a = (1) Binding affinity values are of the format "median (range)" (# (#–#)), "range" (#–#), or "value" (#) depending on the values available. The full sets of values within the ranges can be found in the Wiki code. (2) Binding affinities were determined via displacement studies in a variety of in-vitro systems with labeled estradiol and human ERα and ERβ proteins (except the ERβ values from Kuiper et al. (1997), which are rat ERβ). Sources: See template page.

See also

References

  1. ↑ Bhavnani, BR (January 1998). "Pharmacokinetics and pharmacodynamics of conjugated equine estrogens: chemistry and metabolism". Proceedings of the Society for Experimental Biology and Medicine. 217 (1): 6–16. doi:10.3181/00379727-217-44199. PMID 9421201. S2CID 45177839.
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