I HORMONAL FACTORS 83 1 



males (Figs. 9, 17), tumorigenesis proceeds in the transplants (Kirschbaum et al., 



1956)- 



In preventing X-ray induced ovarian tumor development either estrogen acts 

 directly on the ovary, or the qualitative effect of estrogenic hormone on the pi- 

 tuitary is such that secretion of the tumor-inciting gonadotrophin is inhibited. 

 Androgenic secretion would appear not to have a similar effect on the pituitary 

 according to the latter interpretation. 



Adrenal cortical tumors which secrete sex steroids can be induced by castrating 

 male and female guinea pigs, mice, rats or hamsters (Spiegel, 1939; Woolley, 1939; 

 Houssay et al., 1954) (Figs. 5-7, see p. 826). Genetic factors are important in deter- 

 mining this response to gonadectomy (Figs. 19, 21) since not all strains of mice 

 respond to gonadectomy by cortical tumor development (Frantz and Kirschbaum, 

 1949). The site of gene action determining tumorigenesis is in the adrenal cortex 

 per se (Huseby and Bittner, 1951). 



If sex steroids are administered following gonadectomy, post-castrational ade- 

 nomas or carcinomas do not develop (Woolley and Little, 1946). Since cortisone 

 does not inhibit adenoma development (Monsen, 1952), and since secretion of 

 adenomas can be restored in hypophysectomized-gonadectomized rats by ad- 

 ministration of gonadotrophin, but not ACTH, (Houssay et al., 1955), it appears 

 that gonadotrophic rather than adrenocorticotrophic hormone influences develop- 

 ment and secretion of these experimental post-castrational adrenal cortical over- 

 growths. Many of the carcinomas are hormone-dependent, growing earlier (Fig. 

 20) when transplanted into castrated rather than intact mice of the same inbred 

 strain (Kirschbaum, unpublished; Browning, unpublished). Unlike the mouse 

 and rat cortical neoplasms, sex-hormone secretion of at least certain human 

 tumors of the adrenal cortex is influenced by ACTH (Gallagher, 1957). 



Certain hybrid mice develop pituitary as well as adrenal cortical tumors after 

 castration (Dickie and Woolley, 1949). Since the cortical tumor precedes the 

 pituitary tumors, it has been suggested that the pituitary adenomas appear second- 

 ary to estrogenic stimulation (Figs. 22 and 23) arising from the cortical tumors 

 {Houssay et al., 1955). 



The stimulus to adrenocortical tumor formation in mice appears to be pituitary 

 gonadotrophin. In addition to the evidence cited above (Monsen, 1952) parabiosis 

 experiments (Fig. 24) suggest that preferential utilization of gonadotrophin by the 

 functional testis and ovary may be a factor in inhibiting the genesis of these tumors 

 in normal animals (Monsen and Kirschbaum, 1954). When tumor-bearing mice 

 were placed in parabiosis with intact females, the latter went into estrus due to 

 ovarian stimulation, and the tumor-bearing mice acquired diestrus vaginal 

 smears. With dilution of the gonadotrophin between two hosts the ovaries may 

 have been stimulated preferentially, gonadotrophic but not estrogenic hormone 

 crossing the parabiotic barrier. 



(c) Endocrine tumors following imbalance induced by estrogenic hormone 



Testicular interstitial cell tumors appear in mice of specific inbred strains as 

 a result of administration of estrogenic hormone (Fig. 25) for relatively long periods 

 of time (Hooker et al., 1940; Shimkin et al., 1941; Bonser, 1942). Such tumors 



Literature p. 8yo Text continued on p. 834 



