HORMONAL FACTORS 



833 



Fig. 22. Endocrine factors in the production 

 of adrenal cortical tumors by gonadectomy. 

 Although the administration of cortisone sup- 

 presses the activity of the normal adrenal 

 cortex, adrenal cortical tumors develop in 

 cortisone-treated, gonadectomized mice, in- 

 dicating that gonadotrophic rather than 

 adrenocorticotrophic hormone is involved 

 in the genesis of post-castrational tumors of 

 the mouse adrenal cortex. 



ENDOCRINE INTERRELATIONSHIPS INVOLVED 

 IN ADRENOCORTICftL TUMOR IG ENESIS 



(2) DECREASED 



BLOOD LEVEL 



OF GONADAL 



HORMONE 



(I) OVARIECTOMY - 

 (OR ORCHIECTOMY) 



INCREASED 

 SECRETION OF 



PITUITARY 

 GONADOTROPE 



(4) CORTISONE 

 ADMINISTRATION 



(5) ADRENOCORTICAL 

 TUMORIGENESIS 



ALTHOUGH 

 HYPOPLASIA OF 

 NORMAL CORTEX 



ADRENAL CORTICAL AND PITUITARY 

 TUMORIGENESIS FOLLOWING CASTRATION 



(2) DECREASED 

 BLOOD LEVEL 



OF 

 SEX STEROIDS 



(I) CASTRATION (x) 



(3) PITUITARY HYPERSECRETION 

 OF GONADOTROPE 



(I ADENOMA FORMATION ? ) 

 CO-FACTORS IN PITUITARY 



TUMORIGENESIS— X-RAYS 



NITROGEN MUSTARD 



■-(5) ESTROGEN BLOOD LEVEL 



HIGH— ^•PITUITARY ADENOMAS 



(4) NODULAR HY PERPERPLASIA 

 ADRENAL CORTEX-* CANCER 

 OF ADRENAL CORTEX 



4- 

 DEPENDENT AND INDEPENDENT 



aA /V^ TRANSPLANTS 



^S^T^ HYPERTROPHIED ? 



^ 



\ REPRODUCTIVE TRACT 



M' FR 



-ROM CORTICAL ESTROGEN 



nomas. Some tumors of the adrenal 

 castrated recipients. 



'take" best when 



Fig. 23. Adrenal cortical and pi- 

 tuitary tumors following castra- 

 tion. Experimentally decreased 

 blood level of sex steroids provides 

 the stimulus to hypersecretion of 

 pituitary gonadotrophin. Such 

 hypersecretion may progress to pi- 

 tuitary adenoma formation which 

 probably can be augmented by 

 co-factors (X-rays, nitrogen mus- 

 tard). Since exogenous estrogenic 

 hormone may induce pituitary 

 adenoma formation, it is possible 

 that pituitary tumors may be in- 

 duced by the endogenous estrogen 

 secreted by adrenal cortical ade- 

 transplanted into histocompatible. 



ENDOCRINE INTERRELATIONSHIPS IN ADRENOCORTICAL 

 TUMORIGENESIS STUDIED BY PARABIOSIS BETWEEN 

 TUMOR-BEARING AND INTACT YOUNG FEMALE MICE 



(3) HYPERSECRETION 

 OF PITUITARY 

 GONADOTROPE 



Fig. 24. Preferential utilization 

 of pituitary gonadotrophic 

 hormone as a factor in deter- 

 mining genesis and secretion 

 of mouse tumors of the adrenal 

 cortex. When castrated mice 

 with adrenal cortical adenomas 

 were placed in parabiosis with 

 normal females, the gonado- 

 trope crossed the parabiotic 

 barrier to stimulate the ovaries ; 

 simultaneously the secretion 

 of the tumors of the adrenal 

 cortex was diminished as indi- 

 cated by the diestrus vaginal 

 smear of the tumor-bearing 



parabiont. This suggests preferential utilization of gonadotrope by the ovaries as compared 



with the adrenal cortical adenomas. 



(2) LOW BLOOD 

 LEVEL OF 

 ESTROGEN 



AORENOCORTICAL- 

 ADENOMAS 



(l)OVARIECTOMY 



(4) STIMULATION 

 OF OVARIES 

 BY GONADOTROPE 



(6) DIESTRUS 



VAGINAL SMEAR 



(DUE TO DIVERSION OF 



GONADOTROPE ?) 



Jf TC 



CORNIFIED 

 VAGINAL SMEAR 



graphy. The transplant in the intact mouse began to grow later than in the castrated animal 

 of the same strain. The larger tumor in the castrated mouse was secreting estrogenic hor- 

 mone as indicated by the scrotal hernia (injection of estrogenic hormone induces scrotal 

 hernia). 



Fig, 21. Post-castrational adrenal cortical carcinoma (c). This mouse had been castrated 

 one year before photography. The large carcinoma of the left adrenal was secreting es- 

 trogenic hormone as demonstrated by hypertrophy of the reproductive tract (t). 



Literature p. 8?o 



