Recurrent Jaundice in Pregnancy. IV. Quantitative Determination of Urinary and Biliary Estrogens, Including Studies in Pruritus Gravidarum<sup>1</sup>

Adlercreutz, Herman; Tikkanen, Matti J.; Wichmann, K.; Svanborg, Alvar; Ånberg, Åke

doi:10.1210/jcem-38-1-51

Cited by 41 publications

(7 citation statements)

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“…The values obtained on control days 1 and 2 are for the most part similar to the mean values obtained for the urinary excretion of the same oestrogens in 19 normal subjects, 30-40 weeks pregnant (Adlercreutz et al 1974). How- Values are expressed as mg/24 h and each value represents the mean of two determina¬ tions.…”

Section: Resultssupporting

confidence: 81%

“…However, intestinal interconversion of the various metabolites, about which little is known, could mask such preferential changes. It has been proposed that the conversion of 16a-hydroxyoestrone to oestriol and of 16/?-hydroxyoestrone to 16-epioestriol in the maternal organism partly depends on an intact enterohepatic circulation of oestrogens (Adlercreutz et al 1974); but the changes observed showed no significant trend with regard to these particular metabolic relationships. Similarly, no correlation seems to exist between the effect of ampicillin and the predominant mode of con¬ jugation of particular metabolites in bile.…”

Section: Discussionmentioning

confidence: 99%

“…The determination of 12 urinary oestrogens was carried out by gas-liquid chromatography according to the method of Adlercreutz 8-Litukkainen (1967, 1968 using the modifications described recently (Adlercreutz et al 1974). A critical assessment of the accuracy and precision of this method has recently been published (Adlercreutz 1975).…”

Section: Methodsmentioning

confidence: 99%

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Effect of Ampicillin Administration on the Excretion of Twelve Oestrogens in Pregnancy Urine

Adlercreutz

Martin

Tikkanen

et al. 1975

Acta Endocrinologica

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The excretion of twelve oestrogens in urine, pooled daily from a group of pregnant women, was determined before, during and after ampicillin administration (2 g/day, for 3 days). On the second day of ampicillin administration total oestrogen excretion fell to 67 % of the mean control value, oestriol excretion to 69% and that of the other eleven individual oestrogens to an average of 62 % of the mean control values. In general, on the third day of treatment and on the two post-treatment days this decrease tended to be corrected. The patterns of change in the urinary levels of the individual metabolites provided no clear lead to the basic mechanism of ampicillin impairment of oestrogen excretion. However, as the drug affected all their excretion in more or less the same way as it did that of oestriol, it is possible that ampicillin interferes primarily with their enterohepatic circulation in the mother as has been established with reasonable certainty in the case of oestriol. ·) Present address:

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Section: Resultssupporting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

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Effect of Ampicillin Administration on the Excretion of Twelve Oestrogens in Pregnancy Urine

Adlercreutz

Martin

Tikkanen

et al. 1975

Acta Endocrinologica

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“…The levels of D-ring metabolites increase during pregnancy [6] and may be a key factor in the pathogenesis of intrahepatic cholestasis occurring in pregnant, susceptible women [5]. As a likely mechanism, E17G induces microtubule-independent endocytic internalization of both Abcb11 [7] and Abcc2 [8], [9].…”

Section: Introductionmentioning

confidence: 99%

Sequential Activation of Classic PKC and Estrogen Receptor α Is Involved in Estradiol 17ß-D-Glucuronide-Induced Cholestasis

Barosso¹,

Zucchetti²,

Boaglio³

et al. 2012

PLoS ONE

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Estradiol 17ß-d-glucuronide (E17G) induces acute cholestasis in rat with endocytic internalization of the canalicular transporters bile salt export pump (Abcb11) and multidrug resistance-associated protein 2 (Abcc2). Classical protein kinase C (cPKC) and PI3K pathways play complementary roles in E17G cholestasis. Since non-conjugated estradiol is capable of activating these pathways via estrogen receptor alpha (ERα), we assessed the participation of this receptor in the cholestatic manifestations of estradiol glucuronidated-metabolite E17G in perfused rat liver (PRL) and in isolated rat hepatocyte couplets (IRHC). In both models, E17G activated ERα. In PRL, E17G maximally decreased bile flow, and the excretions of dinitrophenyl-glutathione, and taurocholate (Abcc2 and Abcb11 substrates, respectively) by 60% approximately; preadministration of ICI 182,780 (ICI, ERα inhibitor) almost totally prevented these decreases. In IRHC, E17G decreased the canalicular vacuolar accumulation of cholyl-glycylamido-fluorescein (Abcb11 substrate) with an IC50 of 91±1 µM. ICI increased the IC50 to 184±1 µM, and similarly prevented the decrease in the canalicular vacuolar accumulation of the Abcc2 substrate, glutathione-methylfluorescein. ICI also completely prevented E17G-induced delocalization of Abcb11 and Abcc2 from the canalicular membrane, both in PRL and IRHC. The role of ERα in canalicular transporter internalization induced by E17G was confirmed in ERα-knocked-down hepatocytes cultured in collagen sandwich. In IRHC, the protection of ICI was additive to that produced by PI3K inhibitor wortmannin but not with that produced by cPKC inhibitor Gö6976, suggesting that ERα shared the signaling pathway of cPKC but not that of PI3K. Further analysis of ERα and cPKC activations induced by E17G, demonstrated that ICI did not affect cPKC activation whereas Gö6976 prevented that of ERα, indicating that cPKC activation precedes that of ERα. Conclusion: ERα is involved in the biliary secretory failure induced by E17G and its activation follows that of cPKC.

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“…This probably reflects decreased biliary excretion and impairment of enterohepatic circulation (Adlercreutz, 1974). intrauterine and intrapartum deaths.…”

Section: Disfxjssionmentioning

confidence: 99%

Concealed Placental Abruption in Cholestasis of Pregnancy

Brinsmead

1975

Aust NZ J Obst Gynaeco

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Recurrent Jaundice in Pregnancy. IV. Quantitative Determination of Urinary and Biliary Estrogens, Including Studies in Pruritus Gravidarum¹

Cited by 41 publications

References 0 publications

Effect of Ampicillin Administration on the Excretion of Twelve Oestrogens in Pregnancy Urine

Effect of Ampicillin Administration on the Excretion of Twelve Oestrogens in Pregnancy Urine

Sequential Activation of Classic PKC and Estrogen Receptor α Is Involved in Estradiol 17ß-D-Glucuronide-Induced Cholestasis

Concealed Placental Abruption in Cholestasis of Pregnancy

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Recurrent Jaundice in Pregnancy. IV. Quantitative Determination of Urinary and Biliary Estrogens, Including Studies in Pruritus Gravidarum1

Cited by 41 publications

References 0 publications

Effect of Ampicillin Administration on the Excretion of Twelve Oestrogens in Pregnancy Urine

Effect of Ampicillin Administration on the Excretion of Twelve Oestrogens in Pregnancy Urine

Sequential Activation of Classic PKC and Estrogen Receptor α Is Involved in Estradiol 17ß-D-Glucuronide-Induced Cholestasis

Concealed Placental Abruption in Cholestasis of Pregnancy

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Recurrent Jaundice in Pregnancy. IV. Quantitative Determination of Urinary and Biliary Estrogens, Including Studies in Pruritus Gravidarum¹