ABSTRACT
Foxhounds were made hypercholesterolemic by thyroidectomy and cholesterol feeding. Tracer cholesterol was administered orally, and i.v. and serum samples obtained sequentially for 30 to 89 days at which time the dogs were euthanized and necropsied. Serum and selected tissues were analyzed for cholesterol radioactivity. Kinetics of cholesterol metabolism were calculated. The hypercholesterolemic dogs had large concentrations of cholesterol in the liver. The only kinetic parameter which was correlated with degree of atherosclerosis was the size of pool 2. Absorption of cholesterol was not different in the hypercholesterolemic from control dogs. Tissue cholesterol disappearance rates suggest a third pool of cholesterol having T 1/2 of greater than 200 days. The bile cholesterol kinetics suggest that cholesterol excreted was derived from the very slow pool. Excretion rate and volume appear to be the factors which are most responsible for the inability of the whole animal to maintain homeostasis in cholesterol concentration when a large amount is consumed.
Subject(s)
Arteriosclerosis/etiology , Cholesterol/metabolism , Hypercholesterolemia/metabolism , Animals , Carbon Radioisotopes , Cholesterol/blood , Cholesterol, Dietary/administration & dosage , Diet, Atherogenic , Disease Models, Animal , Dogs , Female , Male , Thyroid Gland/physiology , Tissue Distribution , TritiumABSTRACT
The in vitro effect of 17 alpha-ethinylestradiol (E) and/or medroxy progesterone acetate (P) was determined on their abilities to alter conversion of glucose to lipid by porcine aorta. The combination of steroidal agents EP/HI (combination at high concentration) at a concentration of 9.5 X 10(-9) moles/ml caused a significant (p less than 0.01) reduction in 14C incorporation into total lipid. When the concentration of each hormone was reduced by one-half EP/LO (combination at low concentration) to give a final concentration of 4.8 X 10(-9) moles/ml the incorporation was also significantly reduced (p less than 0.05). The aforementioned reductions were subsequently found to be the result of depressed incorporation of the substrate glucose for the synthesis of phospholipid (PL), triacylglyceride (TG), a combined fraction of free cholesterol, diacylglyceride and free fatty acid (FC+DG+FFA), and cholesteryl ester (CE). The hormones individually had no effect on the incorporation of U14C-glucose into lipid. The study suggests that these oral contraceptives, when administered in pharmacological doses, can depress the conversion of glucose into arterial wall lipid.
