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SPONTANEOUS carcinomas of the adrenal cortex appear to be extremely rare in mice. Slye, Holmes and Wells (1921) found only 4 such tumours in 33,000 autopsies on mice. However, mice of the CE (extreme dilution) strain respond to gonadectomy by developing nodular hyperplasia of the adrenals, followed by adrenal cortical carcinoma in all animals after 6 months (Woolley and Little, 1945a and b). Some strains show little or no adrenal response to gonadectomy, but others (which include DBA and C3H) show an intermediate response (Woolley, Fekete and Little, 1940). In the latter animals, groups of large, vacuolated, lipid-laden cells taking up very little eosin begin to appear in the cortex and such areas of " type B " cells can eventually be observed as white spots on the surface of the adrenal. Later they may become filled with yellow-brown pigment. When these areas have increased until the capsule of the adrenal is raised, the condition is known as nodular hyperplasia. There is secretion of sex hormones, which will cause vaginal cornification and will support the development of mam-mary tumours. Nodular hyperplasia also occurs in intact C3H females towards the end of the second year of life (Pilgrim, 1957). The adrenal hyperplasia in these strains is believed to be a response to increased gonadotrophin which results when the pituitary is released from inhibition by sex hormones following gonadectomy (Hummell, 1954), for it can be prevented by administration of oestrogens or androgens, or by hypophysectomy. It can also be produced in intact mice by uniting them in parabiosis with spayed partners, so that increased gonadotrophin produced by the spayed partner crosses to the also showed that progression of adrenal hyperplasia to carcinoma in CE mice can be prevented by ovarian isografts. Ovarian tumours in mice are also believed to result from a similar disturbance of the mechanisms whereby the gonadotrophin secretions of the pituitary control the secretion of ovarian steroids, which in turn feed back to regulate the secretion of the pituitary. They can be induced in ovaries transplanted to the spleen of a castrated animal, which results in destruction of ovarian steroids by the liver (Biskind and Biskind, 1944), or when the ovary has been damaged by X-rays (Furth and Furth, 1936), or by the administration of triethylene melamine or myleran (Conklin, Upton and Christenberry, 1965), or by 7,12-dimethylbenz(a)an-thracene (Howell, Marchant and Orr, 1954). It has been shown for most of …

Development of adrenal cortical carcinoma in C3H mice following castration and the administration of 7,12-dimethylbenz(a)anthracene.