Estriol glucuronide

Glucose, mandelamine, and hydrochlorothorazide decrease the amount of estriol found when acid hydrolysis is used to release estriol from its conjugate with glucuronic acid in urine. The destruction of estriol in diabetic urine can be monitored by the inclusion of internal standards of labeled estriol glucuronide and reduced by prior dilution of the urine. When glucuronidase is used to release the estriol, the results are not affected when glucose of diabetic urine is present. When this is done the internal standard is not necessary. 

Estrogen, conjugates, see also under Estriol glucuronide and Estrone sulfate, IX, 216-218 formation, IX, 217-218, 233 Estrogens, see also under names of individual compounds action on egg, VIII, 191, 203, 204 activation in tissues, IX, 224 activity,... 

Lampinen-Salomonsson M, Bondesson U, Petersson C, Hedeland M. Differentiation of estriol glucuronide isomers by chemical derivatization and electrospray tandem mass spectrometry. Rapid Commun. Mass Spectrom 2006 20 1429-1440. 

About 30 years ago, the two most important forms of steroid conjugates were isolated, one linked to sulfuric acid (androsterone sulfate, isolated by Venning et o/., 1942), and the other linked to glucuronic acid (pregnanediol glucuronide, isolated by Odell and Martian, 1936, and estriol glucuronide, isolated by S. L. Cohen et al., 1936). 

Estradiol is extensively metabolized by the fetal tissues. After incubation with fetal liver this steroid was transformed into estrone, estriol, 16-epiestriol, and estriol glucuronide (Breucr, 1959 Engel et al., 1962). 

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.

In pregnant women, estriol circulates principally as a double conjugate estriol-3-sulfate, 16a-g ucuronide. The concentration of this diconjugate is 4.5 Mg/100 ml of plasma, representing 40-50% of the total estriol present in blood. The rest of the estriol is composed of estriol monosuifate (25%) and estriol glucuronide (31%) (Touchstone et al., 1963). 

The presence of an important quantity of estriol circulating in maternal blood as 3-suIfate, 16a-gIucuronide permits the suggestion that this conjugate represents an intermediary step between fetal estriol sulfate and maternal urinary estriol glucuronide. This hypothesis is supported by the presence of estriol-3-sulfatc,16 t-gIucuronide in pregnancy urine (Straw et al., 1955). 

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). 

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). 

Amniotic fluid contains estriol in a variety of forms notably free, sulfate, and glucuronide. Therefore the determination is for total estriol content. After extraction, the procedure is the same as just described for the urinary estriol. 

Koenigs-Knorr synthesis of aryl glucuronides. Steroid glucuronides of estrone, 17 /)-estradiol, estriol, and equilenin can be prepared in excellent yield by the reaction of the phenolic steroid with the bromo sugar (I) in toluene using cadmium carbonate as... 

The primary estrogen in premenopausal women is 17-P-estradiol (E2), which is synthesized by developing ovarian follicles. Estradiol is oxidized to estrone (El) and then to estriol (E3). Estrone is also produced in peripheral tissues by aromatization of androstenedione, an androgen precursor that is produced by both the ovaries and the adrenal glands after the menopause, estrone produced in this way becomes the predominant estrogen. All of the estrogens are sulfated and glucuronidated before excretion. 

Isobe et al. [20] extended the seope by analysing both estrogens like estradiol, estrone, and estriol, and their sulfate and glucuronide eonjugates in river water, lake water, and STP samples. SPE in eombination with negative-ion LC-ESl-MS-MS in SRM mode was used. Method deteetion limits between 0.1 and 3.1 ng/1 were reported. While the free steroids and some of the sulfates were deteeted in environmental samples, most of the eonjugates were below the deteetion hmit. 

Figure 54-13 The forms of estriol present in maternal serum, Glucuronidation and sulfation can also occur at the other hydroxyl positions.

Concentrations of estrone, estrioi-3-sulfate, and estriol-3-glucuronide up to lOOOng/mL cross-react less than 0.03% in current assays. 

Pharmacokinetics Most estrogens are well absorbed orally. They tend to be rapidly degraded by the liver during their first pass from the gastrointestinal tract. Metabolites include glucuronide and sulfide conjugates of estradiol, estrone, and estriol. 

Approximately 50% of an exogenous dose of 17p-estradiol undergoes hepatic first-pass metabolism to metabolites that are readily excreted via the kidney, and the remaining 50% is found in bile fluid (9). Much of the material found in bile subsequently enters the intestine, where it is reabsorbed and returned to the liver. Only 10% of an administered dose is found in the feces (5). Both 17p-estradiol and estrone are converted by 16a-hydroxylase to yield estriol (Fig. 46.4A), which is found in the urine as the glucuronide conjugate. 

FIGURE 3.4 Structures of endogenous compounds involved in glucuronidation bile adds, lithocholic add (LA) and hyodeoxycholic acid (HDCA) short chain bile acids, etianic add and isoetianic add, steroid hormones, androsterone, testosterone, estrone, estradiol, estriol. 

The most important estrane derivatives in animals are estradiol, estriol, and estrone. They are transformed to compounds with additional hydroxy and carbonyl groups as well as to suKate esters (D 11) and glucuronides (D 1.2), e.g., estrone-3-0-/3-D-glucuronopyranoside, which are excreted with the urine (E 1). 

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