The pathogenesis of uterine lesions in virgin mice and in gonadectomized mice bearing adrenal cortical and pituitary tumors.

Summary The pathogenesis of the uterine lesions in intact virgin and gonadectomized hybrid mice of the F 1 reciprocal crosses between the DBA and CE strains was studied in animals sacrificed from 15 days to 26 months of age. Cystic hyperplasia of the endometrial glands appeared in both the intact and gonadectomized mice at about 8 months of age. The cystic changes were frequently accompanied by adenomatous hyperplasia of the glandular epithelium. In many of the intact animals these conditions were seen concurrently with invasion of the myometrium by the endometrial glands and surrounding stroma (adenomyosis or myometrial endometriosis). In the gonadectomized group, however, adenomyosis occurred later—not before 14 months of age. Adrenal cortical neoplasms developed in gonadectomized mice by 6–9 months of age. However, the occurrence of uterine lesions in the intact animals indicates that the morphologic changes in the adrenals of the castrates are not necessary per se to the development of the endometrial lesions. The endocrine status of the intact and gonadectomized mice with respect to the activity of the steroid sex hormones was assayed on the basis of the well established cytological changes which are found in the uterus, vagina, and submaxillary glands. Microscopic study of these organs indicated the presence of an endocrine imbalance first manifested at about 6–8 months and persisting to extreme old age, in both the intact and gonadectomized animals. This imbalance was characterized most notably by the continuous, noncyclic, prolonged, and excessive production of estrogen. Since the phenomena are essentially the same in both the intact and gonadectomized mice, the adrenal cortex is presumed to be the source of the aberrant estrogenic hormone.