The effect of estrogen on bile formation in the rat

Forker, E. L.

doi:10.1172/jci106023

Cited by 155 publications

(50 citation statements)

References 30 publications

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“…However, glycine output was not affected by EE in NW or GY/TR Ϫ rats, indicating that the reported increase in glycine transport in canalicular liver plasma membrane isolated from livers of EE-treated rats has no impact on bile formation. Additionally, HCO 3 Ϫ concentrations in bile were not different between the EE-treated and untreated rats, and HCO 3 Ϫ output therefore strongly correlated with bile flow rates, as recently reported by Alvaro et al in normal rats only. 48 So far, we have not been able to identify biliary component(s) that are specifically affected by EE both in NW and GY/TR Ϫ rats and, therefore, can be considered responsible for the reduced bile flow.…”

Section: Discussionsupporting

confidence: 82%

“…Biliary secretion of glycine, a product of intracanalicular GSH hydrolysis, was reduced by about 50% in GY/TR -rats in comparison with NW controls, and remained unaltered after EE treatment (data not shown). Biliary HCO 3 -concentrations were similar in all groups (about 55 mmol/L). Therefore, HCO 3 -output rates varied according to the changes in bile flow.…”

Section: Disposition Of Radiolabeled Eementioning

confidence: 73%

“…Biliary HCO 3 -concentrations were similar in all groups (about 55 mmol/L). Therefore, HCO 3 -output rates varied according to the changes in bile flow. Figure 5 shows the ''classical'' relationship between bile salt output and bile flow in the four experimental groups.…”

Section: Disposition Of Radiolabeled Eementioning

confidence: 73%

“…Biliary cholesterol, phospholipids, and GSH were measured exactly as previously described. 25 Aspartate transaminase, alanine transaminase, bilirubin, amino acid concentrations in bile, and biliary HCO 3 Ϫ were assessed by standard laboratory techniques.…”

Section: Methodsmentioning

confidence: 99%

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Impaired activity of the bile canalicular organic anion transporter (Mrp2/cmoat) is not the main cause of ethinylestradiol-induced cholestasis in the rat

et al. 1998

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To test the hypothesis that impaired activity of the bile canalicular organic anion transporting system mrp2 (cmoat) is a key event in the etiology of 17␣-ethinylestradiol (EE)-induced intrahepatic cholestasis in rats, EE (5 mg/kg subcutaneously daily) was administered to male normal Wistar (NW) and mrp2-deficient Groningen Yellow/Transport-deficient Wistar (GY/TR ؊ ) rats. Elevated plasma bilirubin levels in GY/TR ؊ rats increased upon EE-treatment from 65 ؎ 8.4 mol/L to 183 ؎ 22.7 mol/L within 3 days, whereas bilirubin levels remained unaffected in NW rats. Biliary bilirubin secretion was 1.5-fold increased in NW rats but remained unaltered in GY/TR ؊ rats. Plasma bile salt concentrations remained unchanged in both strains, although hepatic levels of the sinusoidal Na ؉ -taurocholate cotransporting protein (ntcp) were markedly reduced. Biliary secretion of endogenous bile salt was not affected in either strain. A clear reduction of mrp2 levels in liver plasma membranes of NW rats was found after 3 days of treatment. The bile salt-independent fraction of bile flow (BSIF) was reduced from 2.6 to 2.0 L/min/100 g body weight in NW rats with a concomitant 62% reduction of biliary glutathione secretion. The absence of mrp2 and biliary glutathione in GY/TR ؊ rats did not prevent induction of EE-cholestasis; a similar absolute reduction of BSIF, i.e., from 1.1 to 0.6 L/min/100 g body weight, was found in these animals. EE treatment caused a reduction of the maximal biliary secretory rate (S RM ) of the mrp2 substrate, dibromosulphthalein (DBSP), from 1,040 to 695 nmol/min/ 100 g body weight (؊38%) in NW rats and from 615 to 327 nmol/min/100 g body weight (؊46%) in GY/TR ؊ rats. These results demonstrate that inhibition of mrp2 activity and/or biliary glutathione secretion is not the main cause of EE-induced cholestasis in rats. The data indicate that alternative pathways exist for the biliary secretion of bilirubin and related organic anions that are also affected by EE. (HEPATOLOGY 1998;27:537-545.)The synthetic estrogen, 17␣-ethinylestradiol (EE), causes a reversible intrahepatic cholestasis in experimental animals, mainly by reducing the bile salt-independent fraction of bile flow (BSIF). 1 Although EE-induced cholestasis has been claimed to represent a model of cholestasis of pregnancy in humans, 2 the mechanism(s) underlying the reduction in bile flow have not been defined. Suggestions that increased permeability of tight junctions 3,4 and reduced activity of Na ϩ / K ϩ -adenosine triphosphatase (ATPase) at the sinusoidal membrane 5-7 represent primary events in the onset of cholestasis could not be substantiated in more recent studies. [8][9][10][11] Likewise, the relevance of the reported decrease in sinusoidal membrane fluidity after EE treatment remains questionable, because decreased membrane fluidity has also been found in experimental conditions associated with increased bile flow. 11,12 More recently, it was shown that EE differentially affects the activity of transport systems involved in bile formation ...

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Section: Discussionsupporting

confidence: 82%

Section: Disposition Of Radiolabeled Eementioning

confidence: 73%

Section: Disposition Of Radiolabeled Eementioning

confidence: 73%

Section: Methodsmentioning

confidence: 99%

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Impaired activity of the bile canalicular organic anion transporter (Mrp2/cmoat) is not the main cause of ethinylestradiol-induced cholestasis in the rat

et al. 1998

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“…This may be interpreted as meaning that the membrane quality did not change much, at least up to this time. Alternatively, the unchanged B/P ratio with increasing flow in this time period may indicate some increase in permeability (FoRKER, 1969). Thus, the results of the control study are not contradictory to the possibility that the membrane quality changed with time to allow more water and solute influx into the bile per unit bile salt excretion.…”

Section: Discussionmentioning

confidence: 86%

Ursodeoxycholate-induced choleresis in taurine-deprived and taurine-supplemented rats.

Kitani

Kanai

1985

Jpn.J.Physiol

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The effect of i.v. infused ursodeoxycholate (1.2 ,umol/(min 100 g body weight)) was compared in control rats and in taurine supplemented (i.p. administration of a taurine solution) and taurine deprived (oral administration of 13-alanine) rats. In the control rats, the bile water output during the first hr was significantly lower than that of the second hr, while the bile salt output was significantly lower in the second hr. In j3-alanine pretreated rats, the increase in the bile flow in the first hr was more rapid compared to control rats, and the bile flow rate reached a peak earlier. The first hr and total 2 hr bile water outputs were significantly higher in the j3-alanine pretreated rats compared to the corresponding bile flow values of the control rats, while the bile salt outputs were significantly lower than respective control values. In taurine supplemented rats, the increase in bile flow in the second hr was less than in control rats, while the bile salt excretion rate was the highest among the three rat groups. Thus, among these three groups, the bile flow and bile salt excretion rate during the first hr and 2 hr total infusion periods were negatively correlated. On the other hand, a significant positive correlation was observed between the bile flow rate for 1 or 2 hr and bile salt concentration in the liver examined after a 1 or 2 hr bile salt infusion. These results seem most easily explained by our previous thesis that at least part of the bile is produced not by the excretion of bile salt into the bile canaliculus but by its presence inside the hepatocyte (secretory mechanism).

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Secretion of Bile Acids by the Liver and Their Role in the Formation of Hepatic Bile

Wheeler¹

1972

Arch Intern Med

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The effect of estrogen on bile formation in the rat

Cited by 155 publications

References 30 publications

Impaired activity of the bile canalicular organic anion transporter (Mrp2/cmoat) is not the main cause of ethinylestradiol-induced cholestasis in the rat

Impaired activity of the bile canalicular organic anion transporter (Mrp2/cmoat) is not the main cause of ethinylestradiol-induced cholestasis in the rat

Ursodeoxycholate-induced choleresis in taurine-deprived and taurine-supplemented rats.

Secretion of Bile Acids by the Liver and Their Role in the Formation of Hepatic Bile

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