Divergent effects of d-norgestrel on the metabolism of rat very low density and low density apolipoprotein B.

Rats treated with the contraceptive steroid d-norgestrel have lower plasma very low density lipoprotein (VLDL)-triglycerides and higher low density lipoprotein (LDL)-cholesterol than controls. To explain these results, the kinetics of VLDL and LDL turnover were studied by injecting 125I-labeled rat-VLDL and 131I-labeled rat-LDL simultaneously into rats treated with a small dose of d-norgestrel (4 micrograms per day per kg body weight0.75 for 18 days, n = 22) and their untreated controls (n = 22). VLDL- and LDL-apoB specific activity-time curves obtained over 50 hr best conformed to a three-pool model. VLDL-apoB clearance expressed as irreversible catabolic rate (k01) was markedly enhanced in the treated versus control rats (0.57 vs. 0.34 pools hr-1), leading to a marked reduction in VLDL-apoB pool size (270 vs. 420 micrograms). However, VLDL-apoB production rates were similar in the two groups (160 vs. 140 micrograms/hr, respectively). The 125I-labeled apoB specific activity-time curve derived from the catabolism of 125I-labeled VLDL-apoB also showed enhanced clearance in d-norgestrel-treated rats. 125I-Labeled IDL-apoB and 125I-labeled LDL-apoB specific activity-time curves failed to intersect the VLDL-apoB curve at maximal heights, suggesting input of intermediate density lipoprotein (IDL) and LDL independent of VLDL catabolism in both groups. However, the extent of independent LDL-apoB production was similar in both groups. Clearance of 131I-labeled LDL-apoB following injection of 131I-labeled rat-LDL was delayed in the d-norgestrel-treated versus control rats.(ABSTRACT TRUNCATED AT 250 WORDS)