426 



PHYSIOLOGY OF GONADS 



castrated rats with one or two 20-mg. doses 

 of progesterone and observed a slight stim- 

 ulation of mitotic activity in the ventral 

 prostate and seminal vesicles after 55 hours 

 but a pronounced hypertrophy of epithe- 

 lium and connective tissue in both glands. 

 The ventral prostate is more sensitive to 

 progesterone than the seminal vesicles. 



In castrated rats (Price, IMann and Lut- 

 wak-Mann, 1955), treatment with 25 mg. 

 of progesterone daily stimulated the secre- 

 tion of fructose or citric acid in seminal 

 vesicles, coagulating glands, and ventral, 

 lateral and dorsal prostates, and produced 

 histologic changes in the last three glands. 

 The effect, however, was only equivalent 

 to that of about 5 /xg. of testosterone pro- 

 pionate. The lowest threshold to the hor- 

 mone is in the ventral prostate and the 

 highest in the seminal vesicles. Lostroh and 

 Li (1957) found no effects of 0.5 mg. of 

 progesterone daily on the ventral prostate 

 and seminal vesicles of hypophysectomized- 

 castrated adult rats, but the same dose of 

 17a-hydroxy progesterone was the andro- 

 genic equivalent of 4 /xg. of testosterone pro- 

 pionate. It may be noted that the following 

 transformations are involved in the bio- 

 synthesis of testicular androgens: choles- 

 terol —> pregnenolone — > progesterone — > 

 17a-hyclroxy progesterone — > androst-4-ene- 

 3,17-dione -^ testosterone (Dorfman, 

 1957). The slight androgenic actions of pro- 

 gesterone and 17a-hydroxy progesterone 

 may result from their conversion to an- 

 drostane derivatives by extragonadal tis- 

 sues. The findings of Katsh (1950) that 

 progesterone crystals implanted directly 

 into the seminal vesicles of castrated rats 

 have no stimulating influence may be sig- 

 nificant in this regard. 



C. EFFECTS OF ESTROGENS 



Administration of estrogenic hormones to 

 normal males affects the accessory glands 

 both indirectly and directly. The effects fall 

 into three categories: inhibition as evi- 

 denced by weight changes, involution of the 

 epithelium, and loss of secretory activity 

 (attributable to inhibition of pituitary gon- 

 adotro])hin and reduction in endogenous 

 androgen) ; direct stimulation of fibromus- 

 cular tissue; and stimulation of hyi)erplasia 

 and stratified squamous metaplasia of the 



ei)ithelium with possible keratinization. In 

 no case does estrogen induce secretory ac- 

 tivity of epithelial cells. The reduction in 

 seci'etion as determined cjuantitatively (see 

 Section II) may result from castration at- 

 rophy of secretory cells, or from hyper- 

 plastic and metaplastic transformations of 

 the e])ithelium witli resultant loss of normal 

 secretory function. 



The observed responses to estrogen treat- 

 ment in glands of intact and castrated 

 males, and in organ cultures of prostatic tis- 

 sue, represent the dual effects of androgen 

 withdrawal and estrogen addition. The ex- 

 tensive literature on the effects of estrogen 

 and the evidence for so-called antagonis- 

 tic, cooperative and synergistic effects of 

 simultaneous administration of androgen 

 and estrogen have been discussed exten- 

 sivelv (Zuckerman, 1940; Emmens and 

 Parkes, 1947; Ponse, 1948; Bern, 1949b; 

 Burrows, 1949). 



The observation that administration of 

 estrogen to intact male rats causes atrophj- 

 of the accessory glands which is mediated 

 by way of reduction of pituitary gonado- 

 trophin and failure of secretion of testicular 

 hormones was made by Moore and Price 

 (1932). Estrogen-induced atrophy was pre- 

 vented by simultaneous treatment with 

 gonadotrophin or androgen. Direct stimu- 

 lating effects were reported by Freud 



(1933) and David, Freud and de Jongh 



(1934) who observed fibromuscular growth 

 in seminal vesicles of estrogen-treated cas- 

 trated rats and stratification in the duct 

 epithelium of the lateral prostate. Simul- 

 taneous treatment with androgen enhanced 

 the hypertrophic effect of estrogen on the 

 fibromuscular wall of the seminal vesicle 

 but prevented epithelial change in the lat- 

 eral prostate ducts. Korenchevsky and Den- 

 nison (1935) found estrogen stimulation of 

 the muscular layer of the rat seminal vesi- 

 cle with no effect on the epithelium, but in 

 coagulating glands (and to a lesser degree 

 in the dorsal prostate ) there was not only fi- 

 bromuscular hypertrophy but also meta- 

 plastic transformation of the epithelium 

 with stratification; changes in the ventral 

 and lateral lobes were slight and the epi- 

 tiieHum was unaffected. Androgen treatment 

 prevented the jxithologic changes induced 

 by estrogen. Harsh, Overholser and Wells 



