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

Authors

  • Frieder Berr M.D.,

    Corresponding author
    1. Departments of Medicine II and Experimental Surgery, Klinikum Grosshadern, University of Munich, D-8000 Munich, Federal Republic of Germany
    • Medizinische Klinik II, Klinikum Grosshadern, Marchioninistr. 15, D-8000 Munich 70, Federal Republic of Germany
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  • Frans Stellaard,

    1. Departments of Medicine II and Experimental Surgery, Klinikum Grosshadern, University of Munich, D-8000 Munich, Federal Republic of Germany
    Current affiliation:
    1. Free University Hospital, Department of Pediatrics, De Boelelaan 1117, NL 1007 MB Amsterdam, The Netherlands
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  • Alwin Goetz,

    1. Departments of Medicine II and Experimental Surgery, Klinikum Grosshadern, University of Munich, D-8000 Munich, Federal Republic of Germany
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  • Claus Hammer,

    1. Departments of Medicine II and Experimental Surgery, Klinikum Grosshadern, University of Munich, D-8000 Munich, Federal Republic of Germany
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  • Gustav Paumgartner

    1. Departments of Medicine II and Experimental Surgery, Klinikum Grosshadern, University of Munich, D-8000 Munich, Federal Republic of Germany
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Abstract

The mechanism of ethinylestradiol-induced biliary secretion of excess cholesterol, a potential causative factor of cholesterol gallstones, is not yet known. It might be related to altered bile acid metabolism, since the rate of cholesterol and phospholipid secreted into bile is thought to be influenced by the hydrophobicity of the bile acid species secreted. We therefore studied the effect of ethinylestradiol on bile acid metabolism and on secretory relationships between taurocholate and cholesterol/phospholipids in bile. Litter-matched Syrian female hamsters (80 to 100 gm body weight) were injected subcutaneously with either 0.2 ml per day corn oil (controls) or a pharmacologic dose of 5 mg per kg per day ethinylestradiol in corn oil (EE-hamsters; n = 6) for 5 days. On Day 6, bile was collected for 60 min (basal secretory rate) via a bile duct fistula after exclusion of the gallbladder. Then, a graded infusion of taurocholate was given for 110 to 130 min. Secretory rates (nmoles. min−1.−1 liver) for bile acids, cholesterol and phospholipids were determined and their mutual “linkage coefficients” (nmoles of secretory increment per 1 nmole of bile acid secreted) calculated by linear regression analysis. EE-hamsters had higher (p < 0.02) basal secretory rates of cholesterol (0.71 ± 0.21 vs. 0.45 ± 0.10) and phospholipids (5.74 ± 1.04 vs. 4.21 ± 0.73) than controls at comparable bile flow and bile salt secretion rates. Cholic acid pool size and the fractional composition of bile acid species in bile were similar. During graded taurocholate infusion, biliary secretion rates of bile acids were comparable (correlation coefficient = 0.90; p < 0.02) in matched pairs.

EE-hamsters had 60 and 67% higher linkage coefficients for cholesterol/bile acid secretion and phospholipid/bile acid secretion, whereas the linkage coefficient for cholesterol/phospholipid secretion and the y-intercepts of all regressions were not significantly different. In conclusion, ethinylestradiol administration to hamsters increases cholesterol and phospholipid output into bile without increasing the secretion of more hydrophobic bile acids. The unaltered cholesterol/phospholipid linkage suggests that a cholesterol-phospholipid cosecretion mechanism is stimulated.

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