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Adrenal Tumors and Other Pathological Changes in Reciprocal Crosses in Mice

II. An Introduction to Results of Four Reciprocal Crosses^*

G. W. Woolley, M. M. Dickie and C. C. Little

( Roscoe B. Jackson Memorial Laboratory, Bar Harbor, Maine)

Reciprocal crosses of strains A, C3H, DBA, C57BL, CE, and YEL were made, and approximately 1,700 offspring were produced. Half of these were gonadectomized at 1–3 days of age; the rest were maintained as intact control animals. Animals were autopsied at 15 days, 1 month, and at monthly intervals through 24 months of age or beyond. Endocrine and accessory endocrine organs were studied histologically. These studies are reported.

Since this was a pilot experiment and only one animal of each type was examined at each specific age, few general conclusions can be drawn from the results. Several interesting indications of parental influence and genic influence were suggested by the data.

The primary facts were: (a) Characteristic aging changes (x-zone degeneration, lipochrome cell occurrence, benign tumor formation and hyalinization) were observed in the adrenals of intact animals. (b) Adrenal cortical carcinomas were found in gonadectomized animals of all the crosses with evidence of hormone production beyond that found in the parental strains. (c) Structural characteristics in the ovaries (retention and hyalinization of corpora lutea, cyst formation, lipochrome cell deposition, and tumor occurrence) of females of the different crosses were observed and described. (d) Structural changes in the uteri (cystic glandular hyperplasia, adenomyosis, and adenomatous hyperplasia) of intact and gonadectomized females were observed, studied intensively, and reported separately. (e) Pituitary abnormalities (basophilism, and basophile adenomas) occurring in some gonadectomized animals were described in detail in another report.

The data indicate that reciprocal cross differences were concerned most usually with the time of occurrence of various changes, i.e., (a) time of appearance of lipochrome in the adrenals of some of the intact animals, (b) time of occurrence of mammary tumors, (c) time of occurrence of adrenal cortical carcinomas of gonadectomized animals, (d) time of stimulation of the vaginal epithelium of gonadectomized females, and (e) development of mammary gland rudiments in males.

Differences due to genes were more difficult to define, since they were all probably due to the combined action of several genes or alleles of genes. The indications are: (a) in CE hybrids the size of the adrenal, its structure, and the severity of the changes in it following gonadectomy were closely allied with the gene contribution from strain CE. (b) Occurrence of carcinoma in the adrenals of the gonadectomized hybrids was dominant or epistatic to the occurrence of nodular hyperplasia only and was also dominant to the absence of change. (c) Characteristic variations in the ovary, such as the lipochrome cell deposition, hyalinization, and the occurrence of cysts apparently also depend on gene action.

Some speculations on the aspects of hormonal balance and inheritance were made and the value of further investigation of the genetics of the endocrine relationships was discussed.

^* This work has been aided by grants to the Jackson Memorial Laboratory from the Commonwealth Fund, the Anna Fuller Fund, the Jane Coffin Childs Memorial Fund for Medical Research, the National Cancer Institute of the National Institutes of Health, Public Health Service, and the American Cancer Society.

Head, Division of Steroid Biology, Sloan-Kettering Institute, New York, and Visiting Research Associate, Jackson Memorial Laboratory.

Received 10/17/52.