The relationship of the inherited hormonal influence to the production of adrenal cortical tumors by castration.

The work of Loeb (21, 22), Cori (6, 9) and Murray (23, 24) demonstrated that ovariectomy of mice in certain stocks at an early age was associated with a reduction in incidence of spontaneous mammary tumors. Hyperplasia and/or adenoma of the adrenal cortical cells in castrated male and female mice was later described in several inbred stocks (dba, ce, C3H, CBA, NH, Balb) (13, 14, 27, 29). The altered adrenal cortical cells in the castrated mice were linked with gross and histological evidences of estrogenic stimulation of the mammary glands, uterus and vagina. Dorfman and Gardner (10) supported the evidence of physiological activity of adrenal tumors in studies upon ovariectomized mice of the NH strain in which the urinary output of estrogenic substances was increased approximately 4 times over that found in the intact female. Transplants of adrenal tumors (32) and the structure of the submaxillary gland (30) in castrated mice of the extreme dilution stock demonstrated that secretions from the adrenal lesion also contained compounds with androgenic activity. The presence of the adrenal lesions in castrated mice was not correlated with the occurrence of mammary tumors in the stocks mentioned above, in spite of the fact that the original observation of the adrenal lesion occurred coincidentally with the unexpected appearance of mammary tumors in castrated mice (27). The development of mammary tumors in mice is known to be influenced by 3 factors including (a) the genetic susceptibility of the animal, (b) the presence in the milk of the nursing female of an agent transmissible to the offspring, and (c) adequate hormonal stimulation of the mammary gland (3). The tumors in the adrenal cortex