I HORMONAL FACTORS 827 



in this case thyroid deficiency resulting in TSH-secreting pituitary tumors, does 

 not seem to be invariable. Somie '^*I-induced pituitary tumors have gonado- 

 trophic activity and ablation of the adrenal glands does not favor the induction of 

 ACTH-secreting pituitary tumors, rather than gonadotrophic, in whole body- 

 irradiated mice (Furth, personal communication). 



Thyroid tumors have been induced by the administration of goitrogens which 

 create a hormonal imbalance involving the pituitary and thyroid glands (Biel- 

 schowsky, 1949; Griesbach et al., 1945; Morris, 1955). Propylthiouracil inhibits 

 thyroid hormone output of the intact thyroid gland, and as a result secretion of 

 pituitary TSH is increased, with the thyroid gland becoming hyperplastic. Depend- 

 ent neoplasms arising from the hyperplastic thyroid tissues grow upon transplanta- 

 tion in thyroid-deficient but not intact animals (Bielschowsky, 1949; Fig. 61, 

 p. 864). During the course of transplantation the tumors acquire autonomy, now 

 growing in animals with functioning thyroid glands (Morris e/ a/., 1951). Thyroid 

 tumors may occur in rats on low iodine diets; such hypothyroid animals may 

 develop pituitary as well as thyroid tumors (Axelrad and LeBlond, 1955). 



OVARIAN TUMORIGENESIS FOLLOWING TRANSPLANTATION TO SPLEEN 



LOW BLOOD LEVEL OF 



ESTROGEN SECRETED BY OVARY 

 INACTIVATED BY LIVER 



HYPERSECRETION OF 

 GONADOTROPE TO 



ESTROGENIC HORMONE .' \ 'NDUCE OVARIAN TUMOR 



(3) 



OVARIAN TRANSPLANT 



(BECOMES NEOPLASTIC) 



(4) 



OVARIECTOMIZED 



Fig. 8. Endocrine interrela- \,/^ 



tionships involved in ovarian 

 tumorigenesis following trans- 

 plantation to the spleen. 



CASTRATE UTERUS PRIOR 

 • TO DEVELOPMENT OF 

 NEOPLASM IN SPLEEN 



The thyroid tumors resulting from a partial thyroid insufficiency have an origin 

 associated with increased TSH blood levels. If hormonal imbalance per se is 

 responsible for thyroid tumorigenesis, then the carcinogenic stimulus would be 

 TSH. If other factors are involved then the thyroid growth resulting from the 

 action of TSH merely facilitates their action. TSH would then be a "promotor" 

 and not an "initiator" of carcinogenesis. It has been suggested that TSH merely 

 accelerates the growth of latent tumor cells, and does not induce transformation 

 of the thyroid cell from normal to neoplastic (Purves et al., 1951). 



Fig. 7. Undifferentiated tumor (carcinoma) of the adrenal cortex developing in a castrated 

 Ce mouse. In the Ce strain post-castrational adenomas progress to carcinoma, whereas in 

 other strains carcinomas develop only infrequently following post-castrational adenoma 

 formation. 



Literature p. 8yo 



