Mice of the F1 generation reciprocal crosses of JAX strains C57 Black, dba, ce, A and C3H were gonadectomized at 1 to 3 days of age. Virgin females and unmated males were used as control animals. At autopsy, from 14 to 26 months in the experimental groups, pituitary abnormalities occurred. Adrenal cortical carcinomata were also present. The highest incidence of hypophyseal abnormalities occurred in reciprocal hybrids of strains dba and ce. Histological analysis of the hypophyses showed that they were hyperplastic and some were adenomatous. These changes were considered to involve the basophile chiefly and it was decided that the abnormalities were basophilia (possibly adenomas) and focal adenomas. The most striking change, concurrent with the hypophyseal tumors, was the extensive differentiation and over-development of the mammary glands. This change became a criterion for predicting the presence or absence of the hypophyseal changes.

The possibilities as to hormonal activity of the hyperplastic and adenomatous areas of the pituitary were discussed and it was thought that in the combination of pituitary-adrenal disfunction, substances were secreted similar to the gonadotropic and gonadal hormones that reacted most differentially on the mammary glands. The pituitary tumors were compared to Cushing's syndrome in man. The pituitary response, i.e. the appearance of the tumors was, to some extent, a strain-limited factor, as is the pituitary response to hormonal injection.

It was postulated that although the gross pituitary changes were secondary to the changes observed in the adrenal, the fundamental change might have occurred first in the pituitary, reacted on the adrenals, and secretions emanating from the adrenals further reacted on the hypophysis so that gross changes occurred eventually after the adrenals were tumorous.

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This work has been aided by grants to the Roscoe B. Jackson Memorial Laboratory by the Commonwealth Fund, the Anna Fuller Fund, the Jane Coffin Childs Memorial Fund for Medical Research, and the National Advisory Cancer Council.

Animal tissues were collected previous to the fire of October 23, 1947 and most of the tissues were saved. Some detailed notes and slides have been missing since that date.

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