I HORMONAL FACTORS 829 



(b) Hormonal imbalance per se as a factor in inducing neoplasia 



Ovarian tumors can be induced by transplanting the normal rat or mouse ovary 

 to the spleen (Figs. 8 and lo) if no functional ovary exists outside of the portal 

 drainage system, or if adhesions do not form which allow for drainage from the 

 spleen into the systemic circulation (Biskind and Biskind, 1944). Hosts with single 

 ovaries successfully grafted to the spleen are physiologically castrate, ovarian 

 hormone being inactivated in its passage through the liver. As a result the gonado- 

 trophic output of the pituitary gland is increased, and the grafted ovary is hyper- 

 stimulated, such hyperstimulation eventuating in neoplasia. Testicular tumors 

 have been similarly induced by grafting testes into the spleen of castrates. 



Some ovarian tumors induced by transplantation to the spleen are initially 

 hormone-dependent, being transplantable only into the spleens of castrated hosts, 

 an environment simulating that required for induction. Other neoplasms of the 

 ovary, similarly induced, transplant readily to intact hosts (Furth and Sobel, 

 1947; Greene, 1956). 



A hormonal mechanism is apparently involved in the induction of ovarian 

 tumors in mice by X-rays (Lick et al., 1949). Irradiation of a single ovary in mice 

 of a highly susceptible strain does not yield ovarian tumor development if the 

 other ovary is unirradiated and functional (Figs. 1 1-14). Removal of the functional 

 ovary permits the development of a tumor in the irradiated ovary. Local irradia- 

 tion of both ovaries causes bilateral tumorigenesis. 



The pituitary gland becomes hyperactive in secreting gonadotrophin after 

 X-irradiation as a consequence of diminished ovarian hormone output by the 

 irradiated ovaries (Vermande-Van Eck and Chang, 1955). Tumor development 

 would seem to result from stimulation by gonadotrophin of the remaining non- 

 functional ovarian tissues. Such neoplasms may secrete sex steroids (Furth and 

 Sobel, 1947; Greene, 1956). 



The role of gonadotrophins in ovarian tumor development has been further 

 demonstrated by parabiosis experiments (Bielschowsky, 1954). If a normal intact 

 female rat is placed in parabiosis with an hypophysectomized female (Fig. 27, 

 see p. 835), gonadotrophin from the latter crosses the parabiotic barrier to hyper- 

 stimulate the ovaries, for whose steroid secretion the parabiotic barrier is relatively 

 impermeable. Consequently the ovaries are continuously bombarded by gonado- 

 trophin from the pituitary gland of the castrated parabiont, and ovarian tumors 



second ovary remained functional and non-irradiated. These ovaries were photographed 

 sixteen months after exposure to X-rays at which time all irradiated female mice of this 

 strain (Balb/c) have ovarian tumors. The uterus is of a size which indicates that the non- 

 irradiated ovary was functional. 



Fig. 13. Histologic section of irradiated ovary shown in Fig. 1 2. The cortex contains anovular 

 follicles (f). There is no evidence of tumor formation indicating that the non-irradiated 

 functional ovary provided protection against irradiation-induced neoplasia, X 38 

 Fig. 14. Ovarian tumorigenesis. The tumors in the left axillae of these mice developed from 

 non-tumorous irradiated ovaries such as the one shown in Figs. 12 and 13 when they were 

 grafted into castrated females. Photograph 16 months after grafting. This demonstrates 

 that tumorigenesis which had been suppressed for 16 months can proceed when a suitable 

 tumorigenic environment is provided. 



Literature p. 8yo 



