Effect of long-term therapy with an oral contraceptive on some aspects of hepatic lipid metabolism in vitro.

PIP: The effect of Enovid (7.5 mg/kg of food) for both short and long periods of therapy in female Blue Spruce Farm rats was studied. Hepatic release of triglyceride and of cholesterol was measured. Tests were made in vitro. Treatment periods were 4 days of 1 year. The short-term treated group ingested 315 mcg/kg body weight of Enovid daily; the long-term treated group ingested 375 mcg/kg of body weight of Enovid daily. These are about 3 times the daily dose for humans. Animal livers were removed and placed in a perfusion apparatus. The perfusion technique is described. The adrenal glands were also removed and the lipid extract, after being similarly treated in the perfusion apparatus, was tested for cholesterol. Body weights of animals were reduced significantly (p less than .05) by both short- and long-term treatment. The amounts of food consumed were reduced only in the short-term tests. In neither group was change in liver weight found. Bile production was reduced 50% in rats treated 4 days but in those treated 1 year with Enovid no effect was noted when compared with controls. However, in both control and test animals, production of bile after 1 year was reduced by 70-75% as compared with younger animals. Perfusion flow rate in rats treated with Enovid for 1 year was significantly faster (p less than .02) than through livers in the control group. Glucose release was reduced by both short- and long-term Enovid therapy. Reduced food intake may have caused this effect in the short-term therapy. In the group treated with Enovid for 1 year, release of cholesterol and triglycerides into the perfusate was reduced 72 and 38%, respectively. This effect was not observed in the 4-day treated animals. Enovid had no effect on the weights of livers or on the concentration of either triglycerides or cholesterol in hepatic tissue after either form of therapy. No elevation of serum triglyceride was found. A 30% decrease in serum cholesterol was found after 4 days of Enovid therapy. However, in those treated 1 year, and in controls, there was a 100% increase over that of younger animals. Enovid had no effect on the weights of adrenal glands. Total sterol content of adrenal glands from animals treated 1 year was decreased significantly (p less than .05) but not in animals treated only 4 days. Results obtained may be attributed to the metabolic effects of the individual components of Enovid. Further experiments are in progress to examine the effects of each component on hepatic triglyceride transport. Each Enovid tablet contained 5 mg norethynodrel and .075 mg of mestranol.^ieng

Effect of ethynyl estradiol on the secretion of hepatic triglyceride.

The concentrations of triglyceride in the blood of female rats increased 2- and 4-fold during treatment with 5 and 15 mug/kg of ethynyl estradiol, respectively. The rate of secretion of triglyceride increased 66% over controls with livers obtained from the rats administered ethynyl estradiol. Ethynyl estradiol induced a hypocholesterolemia in the donor animals but the secretion of cholesterol into the perfusate from livers obtained from these animal was not affected. Adrenal corticosterone levels were depressed 48% in animals receivint of ethynyl estradiol on the liver or secondary to other hormonal changes.

PIP: The effect of ethinyl estradiol (EE) on the secretion of hepatic triglyceride was studied in female rats. The animals received 5 or 15 mcg/kg body weight of EE for 14 days by subcutaneous injection. Both doses produced hypertriglyceridemia and hypocholesterolemia. Serum triglyceride concentrations increased 2-fold in animals treated with 5 mcg EE (p less than .01) and 4-fold with 15 mcg EE (p less than .005). 5 mcg EE significantly depressed serum cholesterol levels (p less than .05). 15 mcg EE barely affected the already depressed cholesterol levels attained with 5 mcg EE. The rate of secretion, in vitro, of triglyceride increased 66% over control values with EE-treated livers, though the rate of secretion of cholesterol into the perfusate was not affected. EE depressed adrenal corticosterone levels by 48%. The results suggest that EE either acts directly on the liver or interferes with the normal hormonal system regulating triglyceride metabolism.