E217βG; 17β-Estradiol 17β-D-glucuronide; Estra-1,3,5(10)-triene-3,17β-diol 17β-D-glucuronoside
3D model (JSmol)
|Molar mass||448.512 g·mol−1|
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Estradiol glucuronide, or estradiol 17β-D-glucuronide, is a conjugated metabolite of estradiol. It is formed from estradiol 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 estradiol. Glucuronides are the most abundant estrogen conjugates.
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. Estradiol glucuronide can be converted 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 elimination 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 elimination half-life of oral estradiol is 13 to 20 hours whereas with intravenous injection its elimination half-life is only about 1 to 2 hours.
Approximately 7% of estradiol is excreted in the urine as estradiol glucuronide.
Estradiol glucuronide is transported into prostate gland, testis, and breast cells by OATP1A2, OATP1B1, OATP1B3, OATP1C1, and OATP3A1. The ABC transporters MRP2, MRP3, MRP4, and BCRP, as well as several other transporters, have been found to transport estradiol glucuronide out of cells.
Estradiol glucuronide has been identified as an agonist of the G protein-coupled estrogen receptor (GPER), a membrane estrogen receptor. This may be involved in estradiol glucuronide-induced cholestasis.
Estrogen glucuronides can be deglucuronidated into the corresponding free estrogens by β-glucuronidase in tissues that express this enzyme, such as the mammary gland. As a result, estrogen glucuronides have estrogenic activity via conversion into estrogens.
The positional isomer of estradiol glucuronide, estradiol 3-glucuronide, also occurs as a major endogenous metabolite of estradiol, circulating at two-thirds of the levels of estrone sulfate when it reaches its maximal concentrations just before ovulation and during the peak in estradiol levels that occurs at this time.
|Estradiol acetate||C3||Ethanoic acid||Straight-chain fatty acid||2||1.15||0.87||2.8–3.9|
|Estradiol benzoate||C3||Benzenecarboxylic acid||Aromatic fatty acid||– (~4–5)||1.38||0.72||4.5–5.7|
|Estradiol dipropionate||C3, C17β||Propanoic acid (×2)||Straight-chain fatty acid||3 (×2)||1.41||0.71||4.3|
|Estradiol valerate||C17β||Pentanoic acid||Straight-chain fatty acid||5||1.31||0.76||5.8–6.0|
|Estradiol cypionate||C17β||Cyclopentylpropanoic acid||Aromatic fatty acid||– (~6)||1.46||0.69||6.5–7.1|
|Estradiol benzoate butyrate||C3, C17β||Benzoic acid, butyric acid||Mixed fatty acid||– (~6, 2)||1.64||0.61||5.9|
|Estradiol enantate||C17β||Heptanoic acid||Straight-chain fatty acid||7||1.41||0.71||7.0|
|Estradiol dienantate||C3, C17β||Heptanoic acid (×2)||Straight-chain fatty acid||7 (×2)||1.82||0.55||8.1–9.1|
|Estradiol undecylate||C17β||Undecanoic acid||Straight-chain fatty acid||11||1.62||0.62||9.2|
|Estradiol stearate||C17β||Octadecanoic acid||Straight-chain fatty acid||18||1.98||0.51||12.2|
|Estradiol distearate||C3, C17β||Octadecanoic acid (×2)||Straight-chain fatty acid||18 (×2)||2.96||0.34||20.2|
|Estradiol sulfate||C3||Sulfuric acid||Water-soluble conjugate||–||1.29||0.77||0.3–3.8|
|Estradiol glucuronide||C17β||Glucuronic acid||Water-soluble conjugate||–||1.65||0.61||2.1–2.7|
|Estramustine phosphated||C3, C17β||Normustine, phosphoric acid||Water-soluble conjugate||–||1.91||0.52||2.9–5.0|
|Polyestradiol phosphatee||C3–C17β||Phosphoric acid||Water-soluble conjugate||–||1.23f||0.81f||2.9g|
|Footnotes: a = Length of ester in carbon atoms for straight-chain fatty acids or approximate length of ester in carbon atoms for aromatic fatty acids. b = Relative estradiol content by weight (i.e., relative estrogenic potency). c = Experimental or predicted octanol/water partition coefficient (i.e., lipophilicity/hydrophobicity). Retrieved from PubChem and DrugBank. d = Also known as estradiol normustine phosphate. e = Polymer of estradiol phosphate (~13 repeat units). f = Relative molecular weight or estradiol content per repeat unit. g = logP of repeat unit (i.e., estradiol phosphate). Sources: See individual articles.|