ACCESSORY MAMMALIAN REPRODUCTIVE GLANDS 



429 



relative levels of the two hormones. Both 

 affect mitotic activity directly. 



In a comparison of the effectiveness of 

 androgen and estrogen on mitotic activity, 

 Allen (1956, 1958) showed that a dose of 

 16 fjig. of testosterone propionate induces 

 statistically significant increases in mitotic 

 activity of the epithelium of seminal vesi- 

 cles, coagulating glands and ventral pros- 

 tates of castrated mice in 30 to 36 hours. 

 The same dose of estradiol benzoate in- 

 creases mitotic activity in 24 hours in semi- 

 nal vesicles and coagulating glands, but not 

 until 72 hours in ventral prostates. 



Differences in responsiveness to estrogen 

 are evident between rats and mice but in 

 both species there is a gradient of reactivity 

 with coagulating glands showing the most 

 marked changes, seminal vesicles next, and 

 prostatic lobes least. In glands of both spe- 

 cies, the duct epithelium is more sensitive 

 than acinar epithelium and the first ob- 

 servable effects are on urethral ends of 

 ducts. Hyperplastic and metaplastic re- 

 sponses to estrogen occur also to varying de- 

 grees in accessory glands of other mammals 

 — man, monkey, dog, cat, ground squirrel, 

 and guinea pig. Zuckerman (1940) reviewed 

 the effects of estrogen in male and female 

 rodents and other mammals and suggested 

 from the evidence that "stratified squamous 

 proliferation or metaplasia is usually a pri- 

 mary response of tissue in whose develop- 

 ment oestrogen-sensitive entodermal sinus 

 epithelium has played a part." 



On the basis of the pathologic effects of 

 estrogen on the mouse coagulating glands 

 and the protective action of androgen, sev- 

 eral workers originally suggested that be- 

 nign prostatic hypertrophy in man might 

 result from a primary imbalance in the nor- 

 mal ratio of estrogenic to androgenic hor- 

 mones in the male organism (Zuckerman, 

 1936). Further study has not supported this 

 concept. 



D. HORMONAL CONTROL OF SPONTANEOUS 

 PROSTATIC NEOPLASMS 



Spontaneous tumors of the prostate occur 

 in rodents rarely if at all, but benign 

 growths are extremely common in aging 

 dogs and men, and prostatic cancer is a 

 major prol^lem in man. It is noteworthy that 



neoplasms of the seminal vesicles in man 

 are rare (Dixon and Moore, 1952). 



1. Benign Growths 



In the dog, prostatic enlargement which 

 is essentially due to cystic hyperplasia of 

 the epithelium occurs in almost all senile 

 males with functioning testes, but is not 

 found in castrates (Huggins, 1947b). In 

 these prostatic growths, which characteris- 

 tically involve the entire gland, tall colum- 

 nar secretory epithelium is always present 

 in some acini. Canine prostatic hyperplasia 

 is under control of testicular androgens 

 (Huggins and Clark, 1940) and marked in- 

 volution of these tumors as evidenced by 

 their size and secretory activity (see Sec- 

 tion II) can be induced by gonadectomy or 

 treatment with suitable dosages of estrogen. 

 Estrogen overdosage, however, causes pros- 

 tatic enlargement and a metaplasia of the 

 posterior lobe which does not resemble cys- 

 tic hyperplasia. Huggins and Moulder 

 (1945) reported that dogs feminized by es- 

 trogen-secreting Sertoli cell tumors of the 

 testis do not have cystic hyperplasia. The 

 important factors in this pathologic growth 

 seem to be age and testicular androgens 

 (Huggins, 1947b), but prolonged adminis- 

 tration of testosterone propionate to aged 

 castrate dogs results in normal-appearing 

 prostates and not cystic hyperplasia. 



Benign prostatic hypertrophy in man is 

 rarely encountered before the age of 40 

 (Moore, 1943; Huggins, 1947b) but it is 

 extremely common in old men. It differs 

 markedly from prostatic hyperplasia in 

 dogs; the lesions are limited to the medul- 

 lary region of the prostate and are sphe- 

 roidal neoplastic nodules involving, usually, 

 both epithelium and fibromuscular tissue; 

 other nodular types occur but are less fre- 

 quent (Huggins, 1947b; Franks, 1954). The 

 prostatic epithelium is composed of tall 

 secretory cells (Huggins and Stevens, 1940). 

 Despite the fact that castration may be 

 followed by some shrinkage of hypertro- 

 phied human prostate tissue (White, 1893; 

 Cabot, 1896; Huggins and Stevens, 1940), 

 it is generally admitted that this treatment 

 is of little value. Estrogen treatment results 

 in changes in the acini of the inner or medul- 

 lary (periurethral) part of the prostate, 

 and stratification with squamous metaplasia 



