430 



PHYSIOLOGY OF GONADS 



of the duct epithelium, but there is little 

 effect on nodular stroma and acini (Hug- 

 gins, 1947bj. Since benign prostatic hyper- 

 trophy has not been observed in men cas- 

 trated early in life, testicular androgen is 

 presumably involved in its etiology (Hug- 

 gins, 1947b). However, it is doubtful 

 whether androgens are causative agents for 

 this disease. Lesser, Vose and Dixey (1955) 

 found that in men over the age of 45 who 

 had received androgen treatment for non- 

 cancerous conditions, the incidence of be- 

 nign enlargement of the prostate was no 

 greater than in untreated controls. 



2. Prostatic Cancer 



Prostatic cancer is a common disease in 

 elderly men. This carcinoma, which charac- 

 teristically arises in the posterior (outer) 

 region of the prostate, consists of an abnor- 

 mal growth of cells resembling adult pros- 

 tatic epithelium rather than undifferentiated 

 tissue (Huggins, Stevens and Hodges, 1941 ). 

 It was found that these neoplasms are hor- 

 mone-dependent and usually are influenced 

 by anti-androgenic therapy; those which 

 fail to respond are not adenocarcinomas 

 with acini present in the tumor, but are un- 

 differentiated carcinomas with solid masses 

 of malignant cells (Huggins, 1942). How- 

 ever, the two types intergrade and both 

 contain large amounts of acid phosphatase 

 and are considered cancers of adult pros- 

 tatic epithelium. The beneficial effects of 

 castration or estrogenic treatment or both 

 simultaneously, on metastatic carcinoma of 

 the prostate in man were first demonstrated 

 by Huggins and his collaborators (Huggins 

 and Hodges, 1941 ; Huggins, Stevens and 

 Hodges, 1941 ; Huggins, Scott and Hodges, 

 1941 ; Huggins, 1943, 1947a). This discovery 

 was facilitated by the availability of a 

 chemical index of the activity of the neo- 

 plasm, namely, the acid phosphatase activ- 

 ity of blood serum. 



Although testosterone increases the level 

 of serum acid phosphatase in patients with 

 prostatic cancer (Huggins and Hodges, 

 1941 ; Sullivan, Gutman and Gutman, 1942 1 , 

 androgen treatment does not always exacer- 

 bate the growth of the tumor (Trunnel and 

 Duffy, 1950; Brendler, Chase and Scott, 

 1950; Brendler, 1956; Franks, 1958) or may 

 even decrease it (Pearson, 1957). It is ciues- 



tionable if androgens induce prostatic can- 

 cer, inasmuch as their prolonged adminis- 

 tration neither increases the incidence of 

 this disease in man (Lesser, Vose and Dixey, 

 1955) nor induces it in dogs (Hertz, 1951). 



Tlie response of human metastasizing 

 prostate cancer to anti-androgenic therapy 

 is often very dramatic, but neither castra- 

 tion nor treatment with estrogens cures this 

 disease. The tumor may regress for consider- 

 able periods of time, but eventually it recurs 

 and begins to grow again. A small propor- 

 tion of cases do not benefit at all (Huggins, 

 1957; Franks, 1958). Nevertheless, castra- 

 tion and/or estrogen therapy remain the 

 best treatment for prostatic carcinoma in 

 man (Nesbit and Baum, 1950; Huggins, 

 1956; O'Conor, Desautels, Pryor, Munson 

 and Harrison, 1959). 



Huggins and Scott (1945) suggested that 

 the failure of some patients with prostatic 

 cancer to obtain long lasting improvement 

 from castration or estrogen treatment, or 

 the two combined, lay in the secretion of 

 androgenic substances by the adrenal 

 glands. Early attempts to study the effect 

 of bilateral adrenalectomy on human pros- 

 tatic cancer were thwarted by the lack of 

 suitable adrenal cortical steroids for ade- 

 quate substitution therapy. But with the 

 advent of cortisone, bilateral adrenalectomy 

 could be accomplished with ease (Huggins 

 and Bergenstal, 1951, 1952). It seems, how- 

 ever, that adrenalectomy is of limited value 

 to patients with prostatic cancer in relapse 

 after orchiectomy and/or treatment with 

 estrogens (Whitmore, Randall, Pearson and 

 West, 1954; Huggins, 1956; Fergusson, 

 1958). 



E. EFFECTS OF CERTAIN AROMATIC 

 HYDROCARBONS (CARCINOGENS) 



Spontaneous tumors have not been found 

 in the prostate glands of rodents, but tumors 

 can be induced in rats and mice by treat- 

 ment with carcinogenic chemicals such as 

 benzpyrene and metiiylcholanthrene. There 

 lias been considerable interest in inducing 

 such tvnnois and studying their inception 

 and growth, and the iH'lation of steroid hor- 

 mones to their de^•elopment. Such investi- 

 gations have contributed to an understand- 

 ing of early neoi)lastic changes in the rodent 

 prostate, but have had limited applicability 



