Estriol, and estradiol

Estriol is also produced by another pathway in the syncytiotrophoblast cells of the placenta DHEAS from fetal adrenal is converted to 16a-hydroxydehydroepiandrosterone sulfate in the fetal liver, followed by removal of the sulfated chain to produce 16a-hydroxy-dehydroepiandrosterone, which is then aromatized to estriol. Estriol is the predominant estrogen produced during pregnancy, and almost all of tiie estriol and estradiol produced by the placental syncytiotrophoblast enters the maternal circulation. By the 7th week of gestation, the placenta produces the majority of the estrogen in the maternal circulation. 

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). 

On the academic side, W. H. Perkin made mention of unsuccessful experiments directed towards the preparation of benzocyclobutene in 1888. This compound was eventually prepared by H. Finkelstein, a student of J. Thiele, in 1909, as reported in his long-unknown Ph.D. thesis. Benzocyclobutene and biphenylene were also reported by Lothrop in 1941. Tropylium bromide was synthesized in 1891 by Merling, but its structure was only established in 1954 by Doering and Knox. The isolation and structure determination of the aromatic steroids estrone, estriol, and estradiol arrived only in 1929 (E. A. Doissy, A. Bute-nandt), 1931 (G. F. Marian), and 1935 (E. A. Doissy), respectively, with the advent of X-ray crystallography. 

CS Walker, SJ Clark, HH Wotiz. Factors involved in the production of specific antibodies to estriol and estradiol. Steroids 21 259, 1973. 

TLC has been used for the analysis of natural and synthetic estrogens in pharmaceutical preparations. Considerable TLC literature is available on separations involving the three major human estrogens, estrone, estriol, and estradiol-17(3. 

Fig. 1 Fluorescence scan of a chromatogram of ca. 50 ng each of estriol (1), estradiol (2) and estrone (3) per chromatogram zone.

Fig. 2 Reflectance scan (A) and fluorescence scan (B) of a chromatogram track with 1 (ig (A) or 200 ng (B) each substance per chromatogram zone 1 = estriol, 2 = estradiol, 3 = estrone.

In STP effluents, total extractable estrogens and conjugates have been detected at levels up to 1 /jg/L [9,11,26]. Despite the wide variability in terms of removal efficiency reported for different WWTPs, a general trend has been observed with respect to the identity of the compounds most frequently detected in WWTP effluents. Thus, of the various compounds most commonly monitored - namely, estradiol, its metabolites estriol and estrone, and the synthetic estrogen ethynylestradiol - estrone is the most ubiquitous both in WWTP effluents and in environmental waters in general, while the most potent estrogens estradiol and ethynylestradiol have only occasionally been detected [26,40-42]. As for the conjugates, the very few studies that have attempted their determination pointed out estrone sulfates as the most abundant, while glu-curonides are most often found below the limit of detection [26,36,38,39]. 

Estriol, etjuilin, estrone, and estradiol AgNQ, ILO-MeOH (40 60). Octsiiecyl 24 ... 

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). 

Since the neutral molecules of steroid hormones and metabolites are not easily ionized under either APCP or ESI+/ modes, LC-MS/MS is less sensitive when used directly in either APCP or ESI+/ modes, with LOQs at ng/mL level as shown in Table 4 [20, 21, 52], It has been observed that estrone, 16a-hydroxyestrone, 2-methoxyestrone, 4-methoxyestrone, and 2-hydroxy-3-methoxyestrone are sensitive to APCI+ mode, while 2-hydroxyestrone and 4-hydroxyestrone are sensitive to APCI- mode, and even more sensitive to ESI mode [29], Estrone, estradiol, estradiol, and estriol are sensitive to ESI" mode, and testosterone is sensitive to ESP mode [76, 77], Similarly, estrone and estradiol are sensitive to APPI" mode, and testosterone is sensitive to APPI+ mode with LOQs in a range of 1.5-10 pg/mL [22], which are comparable with those steroid hormones and metabolites derivatized with hydroxylamine or dansyl chloride, and detected under ESP mode [2, 8],... 

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... 

Lagana et al. [15] reported the LC-MS analysis of 17-estradiol, estriol, and 17-ethinyl estradiol in STP effluents, using SPE on ENVI-CARB material, positive-ion APCI, and SRM. Recoveries ranging from 84 to 93% were reported. The precision was better than 11 to 8%. Quantitation limits were 0.5 ng/1 for 17-estradiol and 17-ethinyl estradiol, and 1 ng/L for estrone and estriol. 

Benijts et al. [19] applied negative-ion ESI on an ion-trap system for the determination of the estrogens estrone, estradiol, estriol, ethinyl estradiol, and diethylstilbestrol in enviromnental water samples. With manual off-line SPE on 50-ml samples, the deteetion hmits ranged from 3.2 to 10.6 ng/1. 

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. 

Doisy and his associates isolated the sex hormones estrone (1929), estriol (1930), and estradiol (1935). He also isolated two forms of vitamin K and synthesized it in 1936-39. For his work on vitamin K, Doisy was... 

In general most steroids of clinical interest can be measured in saliva. For some steroids, such as cortisol, estriol, and progesterone, the measurement of the sahvary concentration appears to be a reliable indicator of the free concentration in plasma. For others (e.g., testosterone, 17-hydroxyprogesterone, estradiol, and aldosterone) the chnical usefulness of salivary measurements has not yet been fully established. 

The placenta produces several protein and steroid hormones (Figure 54-1). The major protein hormones are CG and placental lactogen (PL). The steroids include progesterone, estradiol, estriol, and estrone. The placenta secretes most of its products into the maternal circulation only small amounts reach the fetal circulation. Close proximity of the maternal blood vessels to the site of placental hormone production may explain some of this preferential accumulation of hormones in the maternal blood circulation. Generally, hormone production by the placenta increases in proportion to the increase in placental mass. Therefore concentrations of hormones derived from the placenta, such as PL, increase in maternal peripheral blood as the placenta increases in size CG, which peaks at the end of the first trimester, is an exception. 

Placental synthesis of estrogens. The placenta lacks the key enzyme necessary for formation of estrogens from cholesterol (CYP 17) and relies on androgenic precursors from the maternal and fetal compartments. The major androgen used comes from the fetal zone of the fetal adrenal this is DHEAS, which is also taken up and metabolized by fetal liver into Iba-hydroxy-DHEAS. The placenta converts DHEAS into estrone (E ) and estradiol (E2) and proces.ses 16a-hydroxy-DHEAS into estriol (Ej). Estrogens enter the maternal circulation and appear in maternal urine as conjugated estrogens. 

The estriol route is the most significant, judging from the fact that estriol is the major urinary estrogen in humans. As its name suggests, estriol contains three hydroxyl groups, two of which are identical to those of estradiol (3, 11 ), but the third is unique to estriol, a 16a-hydroxyl group that is attached to either estrone or estradiol. Estriol formation is increased in obesity and hypothyroidism, and is decreased in hyperthyroidism. Catecholestrogen formation is catalyzed by a 2-hydroxylase that is present in the liver, nerve cells, and other tissues, and both estrone and estradiol... 

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