The inhibition of coronary atherosclerosis by estrogens in cholesterol-fed chicks.

Chronic administration of estrogens parenterally inhibits coronary atherogenesis in cockerels fed a cholesterol-supplemented diet, although no such prophylactic effect was observed against aorta atherogenesis. This protection of the coronary vessels is associated with depression of the plasma total cholesterol-lipid phosphorus ratio toward normal levels consequent upon estrogen-induced hyperphospholipemia. C ORONARY atherosclerosis occurs with significantly greater frequency in the human male than in the female.3' Little is known concerning the basis for this sex differential in susceptibility to coronary atherogenesis. In an attempt to clarify this problem experimentally, we studied the effects of estrogen administration on athero-genesis in the coronary arteries and aorta of cholesterol-fed cockerels. Plasma lipid patterns were simultaneously analyzed in order to ascertain whether any observed morphologic effects might be correlated with concomitant lipid alterations. METHODS Forty-five 1 day old Hy-line cockerels were obtained from a commercial hatchery and reared in a battery brooder. They were fed commercial chick starter mash until they were 7 weeks of age. They were then divided into three groups: Group 1 (control) received mash supplemented with 2 per cent cholesterol and 5 per cent cotton seed oil. Group 2 (experimental) received the same diet plus daily injections of 1 mg. estradiol benzoate (Progynon B, Schering).* Group 3 received plain a diet of mash without cholesterol supplement, and daily injections of 1 mg. estradiol benzoate.t Blood samples were taken and groups of chicks sacrificed at 12, 15 and 20 weeks of age (5, 8 and 13 weeks on the experimental regimens, respectively). Individual blood samples were analyzed for total cholesterol and for lipid phosphorus by the methods of Schoen-heimer and SperryR and of Man and co-workers,9 respectively. At autopsy the hearts and great vessels were inspected for gross atherosclerotic plaques. The lesions were recorded graphically on special forms and graded grossly 0 to 4 according to criteria previously described.7, 10 The hearts were then fixed in 10 per cent formaldehyde. Two blocks were cut from each heart; two frozen sections were then cut from different levels of each block and these were stained with Sudan IV for lipids. When no coronary atheromatous lesions were found in these sections, eight further blocks were cut from these hearts and treated similarly. The hearts were described as either positive or negative for microscopic athero-sclerosis. No attempt was made to grade the lesions. A heart was described as negative when no artery in 20 examined sections showed …