Serum and tissue lipids and glomerulonephritis in the spontaneously hypercholesterolemic (SHC) rat, with a note on the effects of gonadectomy.

A spontaneously hypercholesterolemic male rat, found in the Sprague-Dawley strain, was mated with normocholesterolemic females of the same strain: the male offspring were hypercholesterolemic. By selecting rats according to their plasma cholesterol levels and repeated brother-sister mating, progeny became progressively more hypercholesterolemic--especially the males--when fed a basal low-cholesterol diet. These rats were tentatively given the short name of SHC and have at present been bred to the F14 generation. Hypercholesterolemia in male SHC rats proceeded in two stages: plasma cholesterol rose only slightly during the first stage up to the age of about 10 weeks and then increased progressively in the subsequent stage. Female SHC rats developed a high degree of hypercholesterolemia from the age of 10 months. SHC rats maintained on the basal diet were not obese, but their kidneys and livers enlarged. Histological examination showed that glomerulonephritis developed in the kidney of male SHC rats by the age of 9 months. The liver of these rats was not fatty and contained rather less lipid than usually found in the normal Sprague-Dawley rat. Male and female SHC rats were subjected to gonadectomy at the age of 4 weeks, and were then maintained on the basal diet for 18 weeks. Blood cholesterol was higher throughout the experiment in ovariectomized female SHC rats than in controls, and the renal lesion was correspondingly worse. However, gonadectomy in male SHC rats had no effect on the disease.