Effects of Sex Hormones on Rat Lipoproteins*

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Abstract
Sex hormones (and/or gender) have marked effects on the production and catabolism of plasma lipoproteins in several species. The aim of this work was to characterize the composition and density distribution of the plasma lipoproteins of male and female rats in some detail and to ascertain whether some of the changes seen in plasma were due to hormone action on the liver. Young adult male and female rats of the same age fed a high carbohydrate diet were studied. Experimental animals were castrated. Some animals of each sex were treated with injections of estradiol cypionate (E2, 2.5 μg/day) or testosterone propionate (Tp; 200 μg/day). These injections restored plasma hormone levels of castrated rats to physiological ranges. Controls, sham operated or castrated, were injected with sesame oil. Levels of triglycerides, cholesterol, apoprotein A-I (ApoA-I), ApoB, ApoC-III3, and lipoproteins with densities less than 1,065 in plasma were similar in all groups, but high density lipoproteins (HDL) levels were higher in females and E2-treated castrate males than in males or Tp-treated castrate females. Although the gross composition of the lipoproteins with densities less than 1.065 were similar in all groups, the proportions of ApoC-III1.2 relative to ApoC-III0 and ApoC-III3 were higher in very low density (VLDL) and low density lipoproteins (density, 2-treated castrate males than in those from males or Tp-treated castrate females. The proportions of ApoE relative to ApoC were higher (density, < 1.065) in females. Properties of ApoE relative to ApoA-I and ApoA-IV were also higher in the HDL of females than in that of males. The apoprotein compositions of the HDL of E2-treated castrate males resembled those of females, and the HDL of Tptreated females resembled that of males. Thus, there were sexrelated alterations in the apoprotein composition in the major classes of lipoproteins isolated from plasma. The apoprotein patterns of VLDL (density, vs rat chow) to Sprague-Dawley male rats or those found by us in the hereditarily obese Zucker fatty rat. We conclude that apoprotein patterns may vary with different metabolic perturbations. Two populations of HDL, HDL1 and HDL2, were found (by zonal ultracentrifugation) in the plasma of females and in E2-treated castrate males. Only one population, HDL2, was present in males and Tp-treated castrate females. Since HDL1 contained much more ApoE than did HDL2, the sex-related differences in HDL apoprotein composition could be accounted for by the differences in HDL1 to HDL2 ratios of the various groups. The lipoproteins and apoproteins of prepubertal rats did not differ according to sex. Thus, the gender-related differences in apoprotein compositions and HDL density distributions were due to sex hormones rather than to gender per se.