428 



PHYSIOLOGY OF GONADS 



prostate and there is only slight fragmenta- 

 tion of the Golgi apparatus. In the ventral 

 prostate no epithelial hypertrophy is found 

 but the Golgi network hypertrophies with- 

 out fragmentation or dispersal. The ventral 

 prostate is definitely less sensitive to estro- 

 gen than the other two glands. 



After longer periods of estrogen adminis- 

 tration, Bern (1951) observed fibromuscu- 

 lar hypertrophy of the seminal vesicle and 

 intense alkaline phosphatase activity as in 

 untreated intact males (Table 6.7) ; the 

 epithelium, which is normally negative in 

 enzyme activity, becomes positive and the 

 beginning of metaplastic changes is occa- 

 sionally visible. In the coagulating gland, 

 stratified scjuamous metaplasia with masses 

 of keratin is found and the metaplastic 

 epithelium is strongly alkaline phosphatase- 

 positive; enzyme activity is retained in the 

 stroma but is variable. Bern, Alfert and 

 Blair (1957) reported that the metaplastic 

 coagulating gland epithelium is strongly 

 alkaline phosphatase reactive, virtually 

 PAS-negative, has dense homogeneous 

 RNA concentrations decreasing in amount 

 from base to lumen, and a dense homogene- 

 ous cytoplasmic protein reaction with a 

 gradient of increasing intensity from base 

 to lumen. The enlarged vesicular nuclei of 

 the metaplastic epithelium have lower con- 

 centrations of deoxyribonucleic acid (DNA) 

 than the nuclei of normal epithelial cells. 

 The cytoplasm of these cells is as reactive 

 as normal cells for sulfhydryl groups, and 

 the newly formed keratin is intensely reac- 

 tive; the greatest concentrations of disulfide 

 groups are in superficial keratin. 



In the dorsal prostate (Bern, 1951), es- 

 trogen causes fibromuscular hypertrophy 

 with variable retention of alkaline phosi)ha- 

 tase activity. Metaplastic changes involving 

 basal cell proliferation and stratification be- 

 gin and the metaplastic epithelium is in- 

 tensely alkaline phosphatase active, a rv- 

 versal of the normal reaction. 



Brandes and Bourne (1954), using di- 

 ethylstilbestrol, observed an increase in 

 fibromuscular stroma in coagulating glands. 

 dorsal and ventral prostates, and epithelial 

 hyperplasia and stratification in varying 

 degrees. The most pronounced changes oc- 

 curred in the coagulating gland. The effects 

 of estrogen on Golgi networks, and on PAS 



and acid and alkaline phosphatase reactions 

 are in general similar to the results of cas- 

 tration (Table 6.8). 



Ventral prostate glands have been grown 

 in culture by the watch glass method, with 

 estrogens added to the medium. Lasnitzki 

 (1954, 1958) reported hyperplasia and 

 squamous metaplasia of the epithelium in 

 young i^rostate tissue from C3H mice. In 

 older glands, stimulation of fibromuscular 

 tissue occurred. Franks (1959) using the 

 C57 strain and a different culture medium 

 observed no epithelial hyperplasia and 

 metaplasia, but obtained increases in stroma 

 and muscle. He attributed atrophic changes 

 in the epithelium, which appear more 

 marked in estrogen-treated than in control 

 cultures, to direct inhibition by the hor- 

 mone. Ventral prostate tissue from young 

 mice is more sensitive to estrogen than tis- 

 sue from adult or old males. 



In the dog, Huggins and his collaborators 

 demonstrated the effects of estrogen and 

 combinations of estrogen and androgen on 

 histologic structure and secretion in the 

 prostate (see Section II). Estrogen causes 

 decrease or increase in prostatic size de- 

 pending on the dosage and on the levels of 

 endogenous or exogenous androgen (Hug- 

 gins and Clark, 1940) . Sciuamous metaplasia 

 of the epithelium of ducts and acini occurs 

 with estrogen treatment, but only in the 

 posterior lobe. 



Discussion. The results of estrogen ad- 

 ministration to rats and mice vary with 

 species, age of animal, specific gland under 

 consideration, dosage, duration of treat- 

 ment, and presence or absence of endoge- 

 nous or exogenous androgen. Interpretation 

 of the findings rests on the understanding 

 that androgen directly stimulates mitotic 

 and secretory activity in the epithelial cells. 

 Estrogen inhibits i)ituitary function and 

 thus i-eduees testicular androgen in intact 

 males. It directly increases mitotic activity 

 in th(> epithelium of the accessory glands, 

 and inckices (>pitlielial liy|)erplasia and 

 iiietaphisia, and fibromuscular hyperplasia. 

 W'lietliei' the effects of simultaneous pres- 

 ence of androgen with exogenous estrogen 

 are classified as protective, competitive 

 (antagonistic), or cooperative (synergistic) 

 on the acce.ssoiy glands depends on the 



