Cell cholesterol esters and high-density lipoprotein plasma levels during liver hyperplasia in choline-fed male and female rats

Abstract

Sexual dimorphism exists in the response of rats to lead nitrate, liver hyperplasia occuring earlier and being more pronounced in males. Excess dietary choline in females shifted the growth pattern towards that of males. To determine whether phosphatidylcholine-induced growth modulations could be related to a derangement of cholesterol metabolism, liver accumulation of cholesterol esters and plasma lipoprotein patterns were investigated. In males, lead-induced liver hyperplasia was associated with increased total cholesterol hepatic content, accumulated cholesterol esters and reduced concentration of plasma High Density Lipoprotein (HDL) cholesterol. Females were less responsive to the liver mitogenic signal of lead nitrate; there was no elevation of cholesterol content nor any marked accumulation of cholesterol esters. This is consistent with the lack of change in the plasma levels of HDL cholesterol. Continuous choline feeding displaced the liver cholesterol ester pattern and plasma HDL cholesterol levels in females, and in parallel that of DNA synthesis, towards those of males. Choline was not observed to have any effect in males. These results suggest that the derangement of phosphatidylcholine metabolism induces growth-related changes in cholesterol turnover; they are consistent with the proposal that the intracellular content of cholesterol esters may have a role in regulating liver growth rates.

Figure 1

Effect of lead nitrate on the time-course of ³H-thymidine incorporation into DNA in rats of both sexes. Vertical bars denote S.D.; n = 4. (○) females (•) choline females (□) males (▪) choline-males. ## P < 0. 001 male vs. h 0 after lead nitrate administration *P < 0.01 and **P < 0.001 female vs. male; §P < 0.01 choline-female vs. female.

Figure 2

Effect of lead nitrate on the content of liver esterified CH in rats of both sexes. Vertical bars denote S.D.; n = 4. (○) females (•) choline females (□) males (▪) choline-males. # P < 0. 01 and ##P < 0. 001 male vs. h 0 after lead nitrate administration *P < 0.01 and **P < 0.001 female vs. male; §P < 0.01 and § §P < 0.001 choline-female vs. female.

Figure 3

Elution pattern (min) by HPLC of serum lipoprotein. Peaks: 1, VLDL; 2, LDL; 3, HDL2; 4, HDL3; 5, other serum proteins. a, b, male and female patterns at the beginning of lead nitrate administration, respectively; c, d, male and female patterns 36 h after lead nitrate administration; e, f, choline-male and choline-female patterns 36 h after lead nitrate administration.