Altered apolipoproteins in sex steroid-treated rats

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Effects of sex steroid treatment on plasma triglycerides (TG) were studied in relation to altered plasma lipoprotein composition, plasma postheparin lipolytic activity (PHLA), tissue lipoprotein lipase (LPL), and apoprotein C (apoC) composition and turnover. Adult female rats received parenteral estradiol benzoate (E, 5 μg daily), progesterone (P, 5 mg daily), or the two in combination (E+P) for 21 days. Control rats were administered the sesame oil vehicle alone. E or E+P treatments induced hypertriglyceridemia. Plasma TG, very low density lipoportein (VLDL)-TG, VLDL-protein and high-density lipoprotein (HDL)-protein content were significantly increased 25%–100% compared to control animals. The P regimen alone was without effect on these parameters. While total plasma cholesterol was unchanged by these treatment regimens, HDL-cholesterol was significantly increased in E or E+P groups. Increased plasma TG in E or E+P groups was associated with depressed total PHLA and protamine-sensitive PHLA. However, when parameterial adipose tissue from these animals was incubated with glucose, amino acids, and heparin, release of LPL in the E group was decreased, whereas in E+P it was increased. P treatment resulted in augmentation of both PHLA and LPL activity. Thus, a discrepancy existed between PHLA and LPL release only in the E+P group. When serum from E or E+P groups was added to an LPL assay system using control male rat adipose tissue, LPL activity was suppresed 50%–200% with increasing amounts of serum. In addition, serum from these groups significantly reduced recovery of exogenous PHLA enzyme added to normal rat chylomicrons in vitro, suggesting impaired binding of heparin-releasable enzyme to lipid substrate as one possibility. The inhibitory factor was unrelated to the concentration or lipoprotein form of TG in serum. Apoproteins of VLDL and HDL fractionated by polyacrylamide gel electrophoresis showed increased apoC, arginine-rich peptides, and apoAI in E and E+P rats. Since human apoCII is an activator of LPL and apoCIII is an inhibitor, comparable fractions of rat sera were quantitated from VLDL and HDL following delipidation with tetramethylurea and polyacrylamide gel electrophoresis. Utilizing a double-isotope technique, apoCII and apoCIII turnovers were found to be significantly increased in these two groups in vivo. Moreover, apoCII and apoCIII concentrations were increased in association with reduced apoCIII apoCII ratios in both E and E+P groups. These results contrast to increased ratios reported in human subjects with associated hypertriglyceridemia. We conclude that administration of E alone or combined with P increases the synthesis and serum levels of several apoproteins, including apoC. These perturbations may be responsible for the inhibitory effects of serum from these animals on adipose tissue LPL. These events may modulate TG breakdown in peripheral tissues independent of direct effects of sex steroids on tissue LPL in these rats.