I HORMONAL FACTORS 84 1 



ular androgen did not inhiljit ovarian tumorigenesis in transplanted X-irradi- 

 ated ovaries (Kirschbaum et al., 1956). 



Post castrational adenomas or carcinomas of the adrenal cortex do not develop if ap- 

 propriate doses of either estrogen or androgen are administered, treatment 

 beginning soon after gonadectomy (Woolley and Little, 1946). Such tumor- 

 suppressing doses may alter neither the growth nor secretory activity of certain 

 established cortical tumors (Monsen, 1952). The growth of transplanted "depend- 

 ent" cortical tumors of the Ce strain, in which palpable transplants appear ear- 

 lier in castrated than intact animals, may be delayed by either estrogen or an- 

 drogen (Kirschbaum, unpublished; Browning, unpublished). These inhibiting 

 effects are probably due to suppression of output of pituitary gonadotrophin. 

 Although post-castrational adrenal cortical adenomas may secrete large amounts 

 of estrogenic hormone, the adjustment of the pituitary is such that it is not suppressed 

 in gonadotrophin output, continuing to stimulate the cortical adenomas to secrete 

 sex hormones. Paradoxically, in the rat adrenal, cortical tumors have developed 

 in response to the administration of estrogen (Dunning et al., 1953). 



The induction of post-castrational adrenal cortical tumors of mice is not inhib- 

 ited by administering cortisone in doses large enough to suppress the normal 

 adrenal cortex (Monsen, 1952). Studies on the secretion of sex steroids by human 

 cortical neoplasms indicate dependence on ACTH (Gallagher, 1957), unlike the 

 rat, where resumption of adrenal cortical sex steroid secretion after hypophysectomy 

 could be induced by gonadotrophins but not ACTH (Houssay et al., 1955). 



Pituitary tumors have been reported following castration coupled with either 

 X-irradiation or nitrogen mustard (Gorbman and Edelmann, 1955). Since 

 gonadectomy is essential for tumor development, sex steroids might be considered 

 tumor-suppressive. Pituitary tumors have occurred in mice as a result of gonadec- 

 tomy (Dickie and Woolley, 1949); adrenal cortical neoplasms preceded the ap- 

 pearance of pituitary tumors and it is possible that estrogenic secretion of the 

 cortical adenomas was responsible for pituitary tumorigenesis (Houssay et al., 



1955)- 



Mammary carcinogenesis of mice is inhibited by exogenous androgen (Nathanson 



and Andervont, 1939). Lymphocytic leukeinogenesis is suppressed by androgen, the 

 spontaneous (Murphy, 1944), X-ray (Gardner, 1950) or methylcholanthrene- 

 induced (Kirschbaum et at., 1955) incidence being lower in males of specific 

 strains. Castration has increased susceptibility to spontaneous lymphocytic leuke- 

 mia (Murphy, 1944) and the leukemia-promoting effects of methylcholanthrene 

 (Kirschbaum et al., 1955). Androgen nullifies the leukemogenic activity of 

 exogenous estrogens (Gardner et al., 1940). Androgen prevented X-ray induced 

 lymphocytic leukemogenesis only when administered soon after exposure to 

 X-rays; a delay of six weeks rendered it ineffective (Kaplan and Brown, 1951). 

 Apparently androgen may potentiate granulocytic leukemogenesis in the mouse 

 (Upton and Furth, 1956). Androgenic hormone (testosterone phenylacetate) 

 delays lymphocytic leukemogenesis probably as effectively as cortisone in the high 

 leukemia C58 strain of mice (Kirschbaum and Liebelt, unpublished). 



Conflicting results have been obtained on the effects of cortisone on the car- 

 cinogenic induction of skin cancer. Cortisone has been observed either to inhibit 



Lileralure p. S70 



