Louis C. Fillios

The Importance of Sex in the Variability of the Cholesteremic Response of Rabbits Fed Cholesterol

Cholesterol feeding studies revealed that the wide variability of cholesteremic response of rabbits is in part sex determined. Male rabbits display lower cholesterol levels both before and after cholesterol feeding. Estradiol treatment of selected rabbits fed cholesterol augmented their cholesteremic response; testosterone treatment had an opposite effect. Ovariectomy lowered while orchidectomy augmented the cholesteremic response of rabbits fed cholesterol; castration tended to diminish the wide variability of cholesteremic response previously observed among intact rabbits.

Further Studies on Experimental Atherosclerosis and Dietary Pyrimidines: Orotic Acid, Thiouracil, and Uracil in Male and Female Rats

The comparative potencies of uracil nnd thiouracil in terms of thyroidal changes, hypercholesteremia, azotemia, and incipient atherosclerosis were determined in rats fed cholesterol and cholic acid. Higher dietary levels of uracil were required to produce changes similar to those seen with thiouracil. Certain dietary components related to uracil were also studied. Orotic acid was found to have a dramatic effect on female rats: it favored a markedly lower serum cholesterol level and less cardiovascular sudanophilia. When orotic acid was combined with uracil, the uracil-induced hypercholesteremia and atherogenesis were significantly inhibited, particularly in the females. Orotic acid also protected against the uracil-induced thyroid hyperplasia in these females.

Experimental Production of Colloid Goiter in the Gebus Monkey.

Summary Four Cebus monkeys, 2 males and 2 females, were maintained on a caseincorn oil diet containing 0.5% cholesterol for 86 weeks. For the greater part of this time the diet contained uracil (0.5-0.75%) and during 2 short feeding trials of 3 and 5 weeks duration orotic acid was also included in the diet (0.5%-l%). Uracil produced a further increment in serum cholesterol elevation beyond that due to dietary cholesterol alone as well as an elevation of serum urea. In one female concomitant feeding of orotic acid at the 1% level lowered the serum cholesterol. At autopsy the 2 females demonstrated large colloid goiters while the thyroids of the 2 males showed a mixed picture of both colloid goiter and that of colloid-poor hyperplasia. In one of the males this latter process was extreme and could not be distinguished from early carcinoma. It is assumed that these thyroid changes resulted from ingestion of uracil (or uracil and cholesterol), though the possible role of orotic acid cannot be completely excluded. Speculations on the pathogenesis of the two types of thyroid change are discussed as well as comparisons of the above results with those seen in rats.