Estradiol glucuronidation

Using immobilized -glucuronidase reactors, estriol and estradiol glucuronides have been determined in urine by a column-switching technique (270, 271). Both glucuronides were hydrolyzed by the immobilized enzyme at pH 7. The steroid mixture was subsequently separated by gradient elution on a reversed-phase column, to be finally detected by UV absorbance at 280 nm. In this procedure, the activity of enzyme did not alter even after 150 h continuous run and exposure to a mobile phase containing 10% methanol. When a separate reversed-phase precolumn was inserted in the LC system, additional sample purification and shorter analysis time could be attained (272). 

Estrone glucuronide perfused into the fetoplacental unit through the umbilical vein was metabolized to estradiol glucuronide and to estriol glucuronide ivithout previous hydrolysis. This reaction took place principally in fetal liver (Zucconi et al., 1967a). 

Fig. 19. Principal pathways in tbe transfer of androgen and eatri on conji tes between the amniotic cavity, fetus, placenta, and mother. (1) Possible alternatives (2) suggested glucuronidase activity- Ei estrone Kt estradiol estriol Ei S estrone sulfate Et-S estradiol sulfate Kj-S estriol sulfate Ei-Glu estrone glucuronide Ei-Glu estradiol glucuronide Ej-Glu estriol glucuronide Ej-S,Glu estriol-3-sulfale, IbiF ucuronide DIIA dehydroepiandrosterone I60-IIO-DHA l6a-hydroxydehydro-epiandrosterone DlIA-5 dehydroepiandrosterone sulfate I6a-I10-D1IA-S 16a-hy-droxydehydroepiandrasterone sulfate.

MRP2 (ABCC2) LTC4, bilirubin-glucuronide, estradiol 17 3-glucuronide, dianionic bile salts, anionic conjugates, glutathione disulfide, and others... 

Polyphenols and flavanoids in rat liver microsomal fractions have been demonstrated to inhibit glucuronidation of estrone and estradiol in vitro (Zhu et al, 1998). In addition, flavonoids have also been found to induce phase I and II enzymes in rats including UDP-glucuronosyl transferase (Seiss et al, 1996). However, the effects of phytoestrogens have not been evaluated for either their inhibition or induction of glucuronosyl transferase activity. 

MgCl2 (1 and lOmM) enhanced the glucuronidation activity of HLMs toward estradiol, acetaminophen and morphine [22]. So it is beneficial to include MgCl2 in glucuronidation reactions. However, it may not be feasible to add MgCl2 to a high pH buffer system due to... 

Acetonitrile, methanol and DMSO had no apparent effect on umbelliferone glucuronidation in human hepatocytes at concentration up to 2% [32]. With HLMs or expressed UGTs, inhibitory effects of organic solvents on glucuronidation of 7-hydroxy-4-trifluoromethyl-coumarin (7-HFC) and estradiol generally followed the order acetonitrile > ethanol > methonal > DMSO [33], DMSO did not inhibit estradiol-3-glucuronidation activity at a concentration up... 

Fig. 12.2. Comparison of ATP-dependent transport activity between rats and humans determined in isolated bile canalicular membrane vesicles. Key 1, SN-38 glucuronide (carboxylate) 2, SN-38 glucuronide (lactone) 3, E3040 (6-hydroxy-5,7-dimethyl-2-methyl-amino-4-(3-pyridylmethyl) benzothiazole) glucuronide 4, 170 estradiol-170-D-glucuro-nide 5, grepafloxacin glucuronide 6, leuko-...

Huang, L., Smit, J. W., Meijer, D. K., Vore, M., Mrp2 is essential for estradiol-17beta( beta-D-glucuronide)-induced cholestasis in rats, Hepatology 2000, 32, 66-72. 

Chen ZS, Lee K, Kruh GD. Transport of cyclic nucleotides and estradiol 17-beta-D-glucuronide by multidrug resistance protein 4 Resistance to 6-mercap-topurine and 6-thioguanine. J Biol Chem 2001 276(36) 33747—33754. 

Loe, D.W., Almquist, K.C., Cole, S.P. and Deeley, R.G. (1996) ATP-dependent 17 beta-estradiol 17 - (beta-D-glucuronide) transport by multidrug resistance protein (MRP). Inhibition by cholestatic steroids. Journal of Biological Chemistry, 271, 9683-9689. 

Teo S, Vore M. 1990. Mirex exposure inhibits the uptake of 17beta-estradiol (beta-D-glucuronide), taurocholate, and L-alanine into isolated rat hepatocytes. Toxicol Appl Pharmacol 104(3) 411- 420. 

K. Katayama, Y. Ohshima, M. Tomi, and K. Hosoya. Application of microdialysis to evaluate the efflux transport of estradiol 17-/7 glucuronide across the rat blood-retinal barrier. J. Neurosci. Methods 156 249-256 (2006). 

After administration of estradiol benzoate to calves, the major metabolites found in muscle were estradiol-17 and estrone. The pattern of metabolites occurring in fat was similar to that in muscle. Highest residue concentrations were found in kidney and liver, the major metabolites being identified in kidney including estradiol-17, estradiol-17 -glucuronide, estradiol-17, and estrone. In liver, major metabolites could not be identified but estradiol-17, estrone, estriol, and glucuronides accounted for the remaining radioactivity (2). 

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