ENDOCRINE SECRETION AND TUMOR FORMATION 311 



use reference may be had to many of the original studies. The material is 

 restricted to the mouse. In developing the review, use has been made of the 

 divisions which the mechanics of experimentation have projected into 

 the field. For example, those studies where no hormones have been added 

 from outside of the body have been separated from those where an addition 

 in one form or another has been made. Transplanted tumor studies and 

 evidences of hormone production in tumors are in still separate sections. 



With no outside addition of hormones. — Of all the types of tumors that 

 have been found in experimental mice none have been more extensively 

 studied or more closely related to the endocrine system than those of the 

 mammary glands. That an endocrine factor was involved in the develop- 

 ment was indicated by the experiments of Loeb (55, 56), Lathrop and Loeb 

 (52) and subsequently confirmed by many experimental workers. Three 

 facts stood out. First, mammary tumors developed spontaneously in 

 female but never or very rarely in male mice. Second, the incidence of 

 mammary tumors in female mice varied according to the breeding activity : 

 virgin females had a lower percentage than parous or multiparous females. 

 Third, the tumors of virgin females appeared later than those of breeding 

 females. 



That an endocrine factor was ovarian was indicated by the removal of 

 ovaries at various ages, a technique which caused a decrease in mammary 

 tumor percentage in direct proportion to the time of the ovary removal 

 (55, 52). Experiments by Cori (15) showed that ovariectomy at 16 days of 

 age reduced the percentage to almost zero. Further experiments with 

 ovariectomized mice supported and added to the work of Loeb and Cori 

 (70, 71). 



Many experiments have demonstrated that the ovarian factor is not the 

 sole factor leading to mammary tumor development. The genetic and milk 

 influences are discussed in other chapters of this book. That the endocrine 

 factor need not always be ovarian has recently been demonstrated (87). 

 Following ovariectomy at birth, Jackson Laboratory dilute brown mice 

 developed nodular hyperplasia of the adrenal cortex. This was followed 

 by stimulation of the vagina, uterus and mammary glands. Twenty-seven 

 per cent of the ovariectomized females developed mammary gland tumors. 

 These changes leading all the way to tumor production are not limited just 

 to the dilute brown strain of mice, though they do not occur to the same 

 extent in some of the low tumor strains of mice (86). Recently mammary 

 tumors have appeared in male mice which were castrated at birth. This 

 again followed development of nodular hyperplasia of the adrenal cortex 



