Ethinylestradiol stimulates a biliary cholesterol-phospholipid cosecretion mechanism in the hamster

Berr, Frieder; Stellaard, Frans; Goetz, Alwin E.; Hammer, C.; Paumgartner, Gustav

doi:10.1002/hep.1840080330

Cited by 23 publications

(1 citation statement)

References 27 publications

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“…An interesting observation was the clear increase in phospholipid secretion, which may indicate that the secretion of the two lipid classes (cholesterol and phospholipids) is stimulated in a consonant way. A similar pattern in lipid secretion has recently been reported to occur during treatment with estrogens in a hamster model (31).…”

Section: Discussionsupporting

confidence: 80%

Estrogen-induced gallstone formation in males. Relation to changes in serum and biliary lipids during hormonal treatment of prostatic carcinoma.

Henriksson¹,

Einarsson²,

Eriksson³

et al. 1989

J. Clin. Invest.

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To assess if and by which mechanisms pharmacological estrogen treatment induces gallstone disease, we examined patients with recently diagnosed prostatic cancer randomly allocated to estrogen therapy (n = 37) or orchidectomy (n = 35). According to gallbladder ultrasonography, after 1 yr new gallstones had developed in 5 of 28 estrogen-treated patients, compared with 0 of 26 orchidectomized patients (P = 0.03).Estrogen therapy for 3 mo increased the relative concentration of cholesterol and cholesterol saturation of bile by -30% (n = 10). Serum LDL cholesterol was reduced by -40%, and its relative change related inversely to that of bile cholesterol (R, = -0.77). There were no changes in biliary or serum lipids after orchidectomy (n = 9).Secretion rates of biliary lipids were measured with a duodenal perfusion technique. Patients on chronic estrogen therapy (n = 5) had -40% higher biliary excretion rates of cholesterol than age-matched controls (n = 7). Phospholipid secretion was also higher, but no difference in bile acid secretion was found.We conclude that an increased hepatic secretion of cholesterol results in increased cholesterol saturation of bile and an enhanced rate of gallstone formation during estrogen treatment. The changes in bile cholesterol seem to be related to the induced changes in serum lipoprotein metabolism.

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Section: Discussionsupporting

confidence: 80%

Estrogen-induced gallstone formation in males. Relation to changes in serum and biliary lipids during hormonal treatment of prostatic carcinoma.

Henriksson¹,

Einarsson²,

Eriksson³

et al. 1989

J. Clin. Invest.

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Dietary N–3 Polyunsaturated Fatty Acids Decrease Biliary Cholesterol Saturation in Gallstone Disease

et al. 1992

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Because fatty acid composition of biliary phospholipids Muences cholesterol secretion into bile, we investigated whether replacement of n-1 monounsaturated or n-6 polyunsaturated fatty acids with n-3 polyunsaturated fatty acids in biliary phosphatidylcholines reduces supersaturation with cholesterol and prevents precipitation of cholesterol crystals in bile of gallstone patients. Seven patients with radiolucent gallstones in functioning gallbladders were studied before (control) and after 5 wk of dietary supplementation with marine fish oil (11.3 &day = 3.75 gm 13-3 polyunsaturated fatty acids/day). Duodenal bile was collected for analysis during intravenous infusion of cholecystokinin. Gallbladder emptying in response to cholecystokinin was comparable before and during intake of n-3 polyunsaturated fatty acids. Intake of n-3 polyunsaturated fatty acids increased (p < 0.001) the fractions of eicosapentaenoic and docosahexaenoic acids and decreased the fractions of linoleic (p < 0.001) and arachidonic acids (p < 0.02) in biliary phospholipids. Concomitantly, the molar ratio of cholesterol to phospholipids decreased ( -19%; p < 0.05). As a consequence, the cholesterol saturation index was reduced by -25% (p = O.Ol), from 1.60 f 0.44 to 1.24 f 0.38. However, in uitro nucleation time of duodenal bile was not prolonged. The decrease in cholesterol saturation was not sufficient to prevent nucleation of cholesterol crystals in bile of gallstone patients. In conclusion, our data suggest that cholesterol saturation can be influenced by the fatty acid composition of the phosphatidylcho- This work was supported by grant Be 890/2-2 from the Deutsche Forschungsg e m e k h a f t and by Nycomed Arzneimittd GmbH, Munich, Germany.Part of this work has been published in abstract form (HEPATOLOGY 1990;12:898).

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Mechanism of biliary lipid secretion in the rat: A role for bile acid-independent bile flow?

et al. 1993

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Bile acid-induced lipid secretion was compared in unanesthetized normal control and Groningen Yellow Wistar rats during variations in endogenous bile acid output. Groningen Yellow rats express a genetic defect in the biliary secretion of various organic anions. During a 5-hr period after interruption of the enterohepatic circulation, bile acid secretion decreased from 36.4 +/- 1.8 to 1.9 +/- 0.3 mumol per 30 min in normal control rats and from 37.1 +/- 2.8 to 1.8 +/- 0.2 mumol per 30 min in Groningen Yellow rats, respectively (mean +/- S.E.M., n = 5). The relationship between bile acid secretion and bile flow showed similar slopes (normal control, 8.74 +/- 0.44 microliter/mumol and Groningen Yellow rats, 7.71 +/- 0.42 microliter/mumol) but different y-intercepts (normal control, 243 +/- 8 and Groningen Yellow, 127 +/- 4 microliters per 30 min; p < 0.001), corresponding to a 47% reduction of the bile acid-independent fraction of bile flow in Groningen Yellow rats. During the course of the experiment, the ratio of lipids (phospholipids plus cholesterol) to bile acids increased in both strains more than threefold but was permanently higher in Groningen Yellow than in normal control rats (p = 0.035), implying that Groningen Yellow rats continuously secreted more lipid per bile acid. No differences in bile acid pool composition or in bile canalicular membrane composition and fluidity between the two strains were detected. The results indicate that apart from previously demonstrated factors (bile acid concentration, bile acid composition and hydrophilic organic anion concentration in bile), another parameter affects the efficacy of bile acids to induce biliary lipid secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

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Ethinylestradiol stimulates a biliary cholesterol-phospholipid cosecretion mechanism in the hamster

Cited by 23 publications

References 27 publications

Estrogen-induced gallstone formation in males. Relation to changes in serum and biliary lipids during hormonal treatment of prostatic carcinoma.

Estrogen-induced gallstone formation in males. Relation to changes in serum and biliary lipids during hormonal treatment of prostatic carcinoma.

Dietary N–3 Polyunsaturated Fatty Acids Decrease Biliary Cholesterol Saturation in Gallstone Disease

Mechanism of biliary lipid secretion in the rat: A role for bile acid-independent bile flow?

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