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The Role of Thyroid Function and Food Intake in Experimental Ovarian Tumorigenesis in Mice^*

( Department of Anatomy, Yale University School of Medicine, New Haven, Conn.)

1. One hundred and nine hybrid mice (CC₁) were castrated, and in each an ovary was grafted into the spleen. The mice were then placed on special diets. Eighty-nine of the mice were examined from 11 to 29 months after transplantation.

2. Granulosa-cell tumors, mixed tumors, or luteomas occurred in sixteen of 21 dietary control mice, one of twenty mice fed 0.2 per cent desiccated thyroid powder in the diet, ten of 21 fed 0.2 per cent thiouracil in the diet, five of twelve restricted to two-thirds of the ad libitum food intake, and in twelve of fourteen fed ad libitum after 4–7 months on the restricted diet.
One tumor, of a type previously undescribed, and one tubular adenoma occurred in two female mice fed the desiccated thyroid. The total incidence of ovarian tumors in the thyroid-fed mice was significantly lower than that of any other group.

3. Adrenal cortical hyperplasia occurred in mice of every experimental group. It was most extensive in dietary control and inanition-refed mice.

4. An estrogenic hormone and progesterone were produced in sufficient quantities to cause changes in the uterus despite their passage through the liver, by ovarian tumor-bearing mice in all the experimental groups except the underfed mice; their uteri showed no effects of either hormone. Progesterone effects were present only in mice which showed evidence of estrogen production. Estrogenic effects on the uterus were present in mice without ovarian tumors in association with adrenal cortical hyperplasia.

5. Hepatomas occurred in five of the ten thiouracil-fed mice which did not have ovarian tumors but in only one of the ten such mice with ovarian tumors. The uteri of the ovarian tumor-bearing mice revealed marked estrogenic effects, which were absent in the mice without ovarian tumors. Estrogenic hormone may have inhibited this tumorigenic action of thiouracil.

6. Scrotal hernias occurred in four castrated male mice bearing intrasplenic ovarian tumors.

^* This study was supported in part by grants from the James Hudson Brown Fund of the Yale University School of Medicine, the Jane Coffin Childs Memorial Fund, and the National Cancer Institute of the U.S. Public Health Service (Grant C343).

Received 10/26/53.