Medroxyprogesterone acetate- and ethinylestradiol-induced changes in biliary bile acids of the rat studied by high-performance liquid chromatography.
The effects of subcutaneous administration (5 mg/kg per day) for seven days of medroxyprogesterone acetate (MPA) or 17 alpha-ethinylestradiol (EE) on bile flow, total bile acid output and individual biliary acids have been studied in adult male Wistar rats. Biliary bile acid composition was quantitated by a simple isocratic high-performance liquid chromatographic technique using a C18 reversed-phase radial compression column and refractive index detection. This method revealed that muricholic acids, analysed as taurine and glycine conjugates, constituted a higher proportion of biliary bile acids in the rat than previously observed with gas chromatographic techniques. Marked cholestasis was produced by EE while MPA had little effect on bile flow or total bile acid output. Despite this, both steroids significantly increased the proportion of taurine-conjugated muricholic acids relative to taurocholic acid, although the estrogen had the more pronounced effect. Further study of the hepatobiliary consequences of high doses of MPA would seem warranted in view of the important use of this progestogen for cancer therapy.
Baker
P R
PR
University Department of Surgery, Ninewells Hospital and Medical School, Dundee, U.K.
Vitale
G C
GC
Siow
Y F
YF
D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism*; D002779:Cholestasis / Q000139:chemically induced; D002851:Chromatography, High Pressure Liquid; D004997:Ethinyl Estradiol / Q000494:pharmacology*; D007202:Indicators and Reagents; D008297:Male; D008525:Medroxyprogesterone / Q000031:analogs & derivatives* / Q000032:analysis; D017258:Medroxyprogesterone Acetate; D051381:Rats; D011919:Rats, Inbred Strains
D001647:Bile Acids and Salts; D007202:Indicators and Reagents; D004997:Ethinyl Estradiol; D017258:Medroxyprogesterone Acetate; D008525:Medroxyprogesterone