# Estrone glucuronide

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.
When exogenous estradiol is administered orally, it is subject to extensive first-pass metabolism (95%) in the intestines and liver. A single administered dose of estradiol is absorbed 15% as estrone, 25% as estrone sulfate, 25% as estradiol glucuronide, and 25% as estrone glucuronide. Formation of estrogen glucuronide conjugates is particularly important with oral estradiol as the percentage of estrogen glucuronide conjugates in circulation is much higher with oral ingestion than with parenteral estradiol. Estrone glucuronide can be reconverted back into estradiol, and a large circulating pool of estrogen glucuronide and sulfate conjugates serves as a long-lasting reservoir of estradiol that effectively extends its terminal half-life of oral estradiol. In demonstration of the importance of first-pass metabolism and the estrogen conjugate reservoir in the pharmacokinetics of estradiol, the terminal half-life of oral estradiol is 13 to 20 hours whereas with intravenous injection its terminal half-life is only about 1 to 2 hours.
vte Affinities and estrogenic potencies of estrogen esters and ethers at the estrogen receptors :
| Estrogen | Other names | RBATooltip Relative binding affinity (%)$^a$ | REP (%)$^b$ | REP (%)$^b$ |
| Estrogen | Other names | 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 (EC$_{50}$) 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. |||||
* vte Metabolic pathways of estradiol in humans
* Estradiol
* Estrone sulfate
* Estrone glucuronide
* 2-Hydroxyestrone
* Estrone
* 4-Hydroxyestrone
* 2-Methoxyestrone
* 16α-Hydroxyestrone
* 4-Methoxyestrone
* 17-Epiestriol
* Estriol
* 16-Epiestriol
* 17β-HSD
* EST
* STS
* UGT1A3 UGT1A9
* CYP450
* CYP450
* COMT
* CYP450
* COMT
* unidentified
* 17β-HSD
* unidentified
* Description: The metabolic pathways involved in the metabolism of estradiol and other natural estrogens (e.g., estrone, estriol) in humans. In addition to the metabolic transformations shown in the diagram, conjugation (e.g., sulfation and glucuronidation) occurs in the case of estradiol and metabolites of estradiol that have one or more available hydroxyl (–OH) groups. Sources: See template page.