Experimental studies on hepatocarcinogenesis of synthetic festrogen and progestogen, with special reference to the significance of estrogen-estrogen receptor complex on development of hepatocellular carcinoma.

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Female rats of the Wistar strain, aged 4 weeks, had been daily given a dose of 0.075mg of ethynylestradiol and 6mg of norethindrone acetate (Pill) dissolved in 0.5ml of olive oil through a gastric tube for one year. The levels of total, unoccupied and occupied estrogen receptors of cytosol and nuclei in the liver during carcinogenesis were measured by the exchange assays, and the occupied and total estrogen receptors were confirmed immunocytochemically by using anti-estradiol antibody and anti-estrogen receptor antibody, respectively. The levels of occupied cytosol estrogen receptor were higher in Pill administrated rats than in those with olive oil alone. The levels of occupied nuclear estrogen receptor in the liver were gradually increased during the course of Pill administration, with the development and growth of hyperplastic nodules, especially this levels were extremely high in the area of hepatocellular carcinoma, and these changes were also proved by the immunocytochemical assays. These results suggest that oral contraceptives initiate hepatocarcinogenesis by increasing the estrogen-estrogen receptor complex in the nucleus, directly acting on DNA.
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