Renal clearances of estriol conjugates in normal human pregnancy at term

Young, Bruce K.; Jirku, Helmut; Kadner, Susan; Levitz, Mortimer

doi:10.1016/0002-9378(76)90461-0

Cited by 34 publications

(7 citation statements)

References 13 publications

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“…The lack of correlation between the clearance of oestriol and of creatinine in individual subjects has previously been demonstrated by Carrington et a1 (1970). The renal excretion of these two compounds is regulated by different factors (Swapp et al, 1975;Young et al, 1976). In a recent study in pregnant women we have demonstrated a significant reduction of oestriol clearance caused by physical exercise.…”

Section: Discussionmentioning

confidence: 89%

“…In urine, oestriol-16 a-glucosiduronate is by far the most abundant conjugate, accounting for approximately 70 per cent of the total followed by oestriol 3-glucosiduronate, oestriol-3-sulphate, 16a-glucosiduronate and oestriol-3-sulphate. The relative contribution of each conjugate to the total is far more stable in urine than in plasma and the different conjugates have different renal clearances (Swapp et al, 1975;Young et al, 1976). Furthermore, the biological half-life of the oestriol sulphoconjugates by far exceeds that of the glucosiduronate fraction, this is mainly due to the strong binding to albumin of the former (Goebelsman et al, 1973;Klopper et al, 1978).…”

Section: Discussionmentioning

confidence: 99%

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Urinary Excretion of Oestriol and Plasma Levels of Unconjugated and Total Oestriol During Late Uncomplicated Pregnancy

Carlström

LlNDBERG

1980

BJOG

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Summary Plasma levels of unconjugated and total oestriol and urinary excretion of oestriol were measured in ten healthy women with uncomplicated pregnancy and with normal renal function. A significant correlation between plasma total oestriol and urinary oestriol was found in five out of ten patients and between plasma total and unconjugated oestriol in only four out of ten patients. When the data from the ten patients were combined there were significant correlations between urinary oestriol and the two plasma oestriol species as well as between plasma unconjugated and total oestriol. The mean urinary oestriol excretion correlated significantly with the mean urine volume. No significant correlation was found in the individual subjects between oestriol clearance and creatinine clearance, but the combined data from the ten patients yielded a highly significant correlation. The differences within or between days was highest for plasma unconjugated oestriol and lowest for urinary oestriol/mmol of creatinine. Over a three to four day period, a drop of 20 per cent in urinary oestriol/mmol of creatinine, 25 per cent in urinary oestriol/24 hours, 35 per cent in plasma total oestriol and 40 per cent in plasma unconjugated oestriol do not necessarily indicate fetal danger.

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Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Urinary Excretion of Oestriol and Plasma Levels of Unconjugated and Total Oestriol During Late Uncomplicated Pregnancy

Carlström

LlNDBERG

1980

BJOG

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“…E~-3-S is found in higher concentrations in type 1 than in type 2 cysts, and a positive correlation between this conjugated estrogen and DHEA-S was observed [60]. E~-3-S is also concentrated at very high levels [59], even exceeding those found in circulating plasma during pregnancy [61].…”

Section: Androgens and Estrogens Sulfoconjugated In Hbcfmentioning

confidence: 94%

Biochemical study of cyst fluid in human breast cystic disease: a review

Enriori¹,

Novelli

Cremona³

et al. 1992

Breast Cancer Res Tr

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Gross cystic disease of the breast may sometimes indicate an increased risk of breast cancer. Biochemical analysis of the cyst fluid could suggest which cysts are associated with breast cancer risk, as well as providing insights into the pathophysiology of this condition. The Na+/K+ ratio appears to be associated with the histological classification of the cyst. Sulfoconjugated estrogens and androgens, especially DHEA-S, are often found at high levels. A number of gross cystic disease fluid proteins (GCDFPs) have been described, and several polypeptide growth factors including EGF and IGF-I are frequently found. It is hoped that biochemical analysis of these components of breast cyst fluids will shed further light on the role of gross cysts in relation to breast cancer.

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“…Estriol is considered to be an end product of estrogen metabolism (endogenous and exogenously administered) and it is extensively conjugated directly to E3-3G and E3-16G in the intestine, or only to E3-16G in the liver [1,5,46]. After oral administration of estriol, the glucuronides circulate at relatively high levels, almost 1000-fold higher than the parent compound, until they are finally excreted into urine [1,47,48]. The enterohepatic circulation of estriol conjugates does not seem to be as extensive as for estradiol and estrone conjugates [5,6,49].…”

Section: Transport and Disposition Of E3-3g And E3-16gmentioning

confidence: 99%

Efflux transport of estrogen glucuronides by human MRP2, MRP3, MRP4 and BCRP

Järvinen

Deng

Kidron

et al. 2018

The Journal of Steroid Biochemistry and Molecular Biology

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Estrone, estradiol and estriol are endogenous human estrogens that are rapidly conjugated with glucuronic acid in both intestinal and hepatic epithelial cells. The resulting glucuronides, estrone-3-glucuronide (E-G), estradiol-3- and 17-glucuronides (E-3G and E-17G), as well as estriol-3- and 16-glucuronides (E-3G and E-16G) are found in human plasma and urine. Unlike E-17G, the efflux transport of other estrogen glucuronides by human transporters has not yet been investigated comprehensively. We have studied the transport of E-G, E-3G, E-3G, E-16G and estrone-3-sulfate (E-S), another important estrogen conjugate, using the vesicular transport assay with recombinant human MRP2, MRP3, MRP4, MDR1 and BCRP that were expressed in insect cells. The transport screening assays revealed that whereas E-S was a good and specific substrate for BCRP, the less transporter-specific conjugates, E-G and E-3G, were still transported by BCRP at 10-fold higher rates than E-S. BCRP also transported E-16G at higher rates than the studied MRPs, while it transported E-3G at lower rates than MRP3. MRP2 exhibited lower or equal transport rates of E-G, E-3G, E-3G and E-16G in comparison to MRP3 and BCRP in the screening assays, mainly due to its high K values, between 180 and 790 μM. MRP3 transported all the tested glucuronides at rather similar rates, at K values below 20 μM, but lower V values than other transporters. In the case of E-3G, MRP3 was the most active transporter in the screening assay. MRP4 transported only E-16G at considerable rates, while none of the tested estrogen conjugates was transported by MDR1 at higher rates than control vesicles. These new results, in combination with previously reported in vivo human data, stimulate our understanding on the substrate specificity and role of efflux transporters in disposition of estrogen glucuronides in humans.

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Renal clearances of estriol conjugates in normal human pregnancy at term

Cited by 34 publications

References 13 publications

Urinary Excretion of Oestriol and Plasma Levels of Unconjugated and Total Oestriol During Late Uncomplicated Pregnancy

Urinary Excretion of Oestriol and Plasma Levels of Unconjugated and Total Oestriol During Late Uncomplicated Pregnancy

Biochemical study of cyst fluid in human breast cystic disease: a review

Efflux transport of estrogen glucuronides by human MRP2, MRP3, MRP4 and BCRP

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