Cholestyramine treatment during pregnancy in the rat results in hypercholesterolemia.
Timed pregnant (8 days) Sprague-Dawley rats were fed ground stock diet (CON) or ground stock diet with 4% cholestyramine (CTR) until day 20 of gestation. Animals in both groups gained weight equally well during the study period (CON (n = 7), 308 +/- 7 g; CTR (n = 6), 315 +/- 7 g, mean +/- SEM). At the end of the study period, plasma cholesterol in the CTR group was significantly greater than that in the control group (CON n = 7, 91 +/- 4 mg/dl; CTR (n = 6), 108 +/- 5 mg/dl, P less than 0.05). The fecal excretion of both neutral steroids and bile acids, studied for 3 days between days 15 and 18 of gestation, was significantly enhanced by CTR treatment. (Neutral steroids: CON, 3.9 +/- 0.3; CTR, 10.4 +/- 0.3, P less than 0.05. Bile acids: CON, 7.6 +/- 0.4; CTR, 25.8 +/- 1.7, P less than 0.05, mg/100 g body wt/day). Bile acid pool size, measured at day 20 of gestation, however, was not significantly different. Consistent with these results was the finding that hepatic cholesterol 7 alpha-hydroxylase activity (the rate-limiting enzyme of bile acid biosynthesis) measured at day 20 of gestation was significantly enhanced by CTR treatment (CON (n = 4), 14.7 +/- 1.7; CTR (n = 4), 34.8 +/- 3.3, pmoles/mg/min, P less than 0.05). The atypical finding of hypercholesterolemia, despite the CTR-induced enhanced turnover of cholesterol, may be due to changes in the homeostatic mechanisms of cholesterol and bile acid metabolism during pregnancy.
D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D002790:Cholesterol 7-alpha-Hydroxylase / Q000378:metabolism; D002792:Cholestyramine Resin / Q000633:toxicity*; D005243:Feces / Q000032:analysis; D005260:Female; D005865:Gestational Age; D006937:Hypercholesterolemia / Q000139:chemically induced* / Q000150:complications / Q000378:metabolism; D008099:Liver / Q000201:enzymology; D011247:Pregnancy; D011248:Pregnancy Complications / Q000139:chemically induced* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013256:Steroids / Q000378:metabolism
D001647:Bile Acids and Salts; D013256:Steroids; D002792:Cholestyramine Resin; D002784:Cholesterol; D002790:Cholesterol 7-alpha-Hydroxylase