830 



THE CARCINOGENIC STIMULUS 



II 



are induced. Their estrogenic secretion may in turn excite adenomatous trans- 

 formation of the pituitary of the intact parabiont; mammary gland stimulation 

 results from the mammotrophic secretion of the pituitary tumor. 



Although hormonal imbalance per se might be responsible in specific experi- 

 mental situations for the development of ovarian tumors, it appears that excessive 

 stimulation of the ovaries by gonadotrophin might not be necessary for carcinogen- 

 esis. There is no clinical evidence that hypo-ovarianism stimulating excessive 

 output of pituitary gonadotrophins precedes human ovarian carcinogenesis. 



INHIBITION OF IRRADIATION-INDUCED OVARIAN 

 TUMORIGENESIS BY OVARIAN SECRETION 



(2) NORMAL 

 LEV"iL OF 

 OVARIAN 

 HORMONE 



(I) FUNCTIONAL 

 OVARY 



(3) NORMAL SECRETION 

 OF PITUITARY 

 GONADOTROPE 



(4) NO 

 TUMORIGENESIS 

 IN IRRADIATED 

 OVARIAN GRAFT 



Fig. 15. Endocrine mechanism whereby 

 functional ovaries inhibit tumorigenesis in 

 an X-irradiated ovarian transplant. 



INHIBITION OF IRRADIATION-INDUCED OVARIAN 

 TUMORIGENESIS BY OVARIAN GRAFTS 



Fig. 16. Mechanism of inhibition 

 of ovarian tumorigenesis byfunc- 

 tional ovarian transplants. 



(3) OVARIAN 

 ESTROGEN IN 

 BLOOD 



(2) FUNCTIONAL 

 OVARIAN 

 GRAFT 



(I) IRRADIATED 

 OVARIES 



(4) NORMAL SECRETION 

 OF PITUITARY 

 GONADOTROPE 



(5) INHIBITION 

 OF OVARIAN 

 TUMORIGENESIS 



Carcinogenic hydrocarbons may induce ovarian tumors in intact female mice 

 whose pituitary gonadotrophin output is probably within normal limits (Howell 

 et al., 1954). 



If irradiated ovaries are transplanted to intact females (Fig. 15) tumorigenesis 

 is inhibited by ovarian secretion (Kaplan, 1950b). Functional ovarian grafts made 

 following ovarian irradiation in situ (Fig. 16) also inhibit ovarian tumorigenesis 

 (Kirschbaum et al., 1956). Although androgenic hormone (exogenous) inhibits 



IRRADIATION INDUCED OVARIAN TUMORIGENESIS 

 IN THE PRESENCE OF NORMAL LEVEL OF 

 ANDROGENIC HORMONE 



(2) NORMAL 

 LEVELOF 

 ANDROGENIC 

 HORMONE 



(I) FUNCTIONAL-AaA 

 TESTIS ^^^<f 



(3) NORMAL SECRETION 



(4) IRRADIATED 

 OVARIAN GRAFT 



BECOMES 

 NEOPLASTIC 



Fig. 1 7. X-ray induced ovarian tumorigenesis 

 in grafts into intact male mice. 



ovarian tumor development in splenic (ovarian) transplants, X-ray induced ovarian 

 tumorigenesis is not similarly inhibited (Gardner, 1 950) . When irradiated ovaries 

 of inbred mice are transplanted to intact genetically related (histocompatible) 



