I HORMONAL FACTORS 845 



resulted from the imbalance brought about by withdrawal of target organ 

 secretion. Pituitary trophic hormones may be necessary for the growth of "hormone 

 responsive" {e.g. adrenal) tumors. Change in the sensitivity of a target tissue {e.g. 

 X-irradiated transplanted ovary in intact male mouse) may result in tumorigenesis 

 with normal levels of trophic hormone (Kirschbaum et al., 1956). 



Mammo trophic hormone of the pituitary gland, secreted as a result of the action 

 of estrogen on the pituitary, may be a factor as potent as any in mammary tu- 

 morigenesis (Miihlbock, 1956). 



Following hypophysectomy hepatic tumorigenesis did not result from feeding 

 hepatic carcinogens (Griffin et al., 1955). Susceptibility could be restored by ad- 

 ministration of growth hormone, but not ACTH to hypophysectomized rats. 

 Thyroidectomy had a similar effect on hepatic carcinogenesis when acetylamino- 

 fluorene was fed (Bielschowsky and Hall, 1953). Since acidophiles are absent from 

 the hypophysis of thyroidectomized rats, growth hormone deficiency has been 

 suggested as responsible for the results with thyroidectomy. The incidence of 

 hepatic tumors was reduced when rats fed acetylaminofluorene were made hy- 

 pothyroid with thiouracil (Paschkis et al., 1948). 



Initial experiments suggested that hepatic tumors can be induced in hy- 

 pophysectomized rats receiving ACTH (Griffin et al., 1955); rats were made re- 

 fractory to the tumor-inciting action of butter yellow by adrenalectomy (Syme- 

 onidis et al., 1951). The influence of sex steroids on hepatic tumor incidence has 

 been discussed elsewhere. Whether the accelerating effisct of androgenic hormone 

 is via effects on other endocrine organs has not been determined. 



Lymphatic tissue regenerates after irradiation in the absence of the pituitary 

 gland. Hypophysectomy did not inhibit leukemogenesis, and the induction of 

 leukemia was prevented in X-irradiated mice by shielding bone marrow (Nagareda 

 and Kaplan, 1955). 



Pituitary growth hormone has been held responsible for the development of a 

 variety of rat tumors {Vloon et al., 1950 a, b,c, 1951, 1952, 1955, 1956). Although 

 the sarcogenic effects of methylcholanthrene were reported reduced by hy- 

 pophysectomy (Moon et al., 1955), other investigations indicate that initiation is 

 either not altered or only delayed (Noble and Walters, 1954); the subsequent 

 growth rate of the neoplasms is reduced (Agate etal., 1955). Carcinogenesis by 9,10- 

 dimethyl-i,2-benzanthracene occurred when hypophysectomized rats were given 

 growth hormone, but not ACTH (Moon et al., 1956). 



Although growth hormone increased the growth rate of a transplanted tumor, 

 the influence was comparable to that upon general body growth (Smith et al., 

 1952). Growth of two transplanted tumors was not influenced by purified growth 

 hormone (Schulman and Greenberg, 1949). Transplants of the Walker sarcoma 

 "took" in hypophysectomized rats (Talalay et al., 1952), but growth was inhibited 

 by one-third (Rock et al., 1955). The seeding of mouse tumor cells was augmented 

 after intravenous inoculation if the recipients were treated with growth hormone 

 before and after tumor transfer (Wood et al., 1955). 



In all hypophysectomy experiments inanition effects must be differentiated from 

 hormone withdrawal (Ball and Samuels, 1938; Korteweg and Thomas, 1949). The 

 anabolic influence of growth hormone depends upon adequate food intake. In spite 



Literature p. 8yo 



