MAMMALIAN TESTIS 



34; 



velopment of the testis of the iiinnature rat 

 was arrested by prolonged injections of this 

 steroid. Effects from desoxycorticosterone 

 are not evident in adrenalectomized animals 

 (Migeon, 1952). Adult rats show atrophy of 

 both the tubular apparatus and the Leydig 

 cells (Naatanen, 1955; Selye and Albert, 

 1942a, b). Maintenance of spermatogenesis 

 after hy])ophysectomy was described by 

 Overzier (1952). 



Because cortisone even in massive doses 

 has little effect on the testis, it would seem 

 unlikely that ACTH would have any dra- 

 matic effects. Li and Evans (1947) repoi'ted 

 that ACTH depresses testicular weight and 

 the weight of the accessories in young rats, 

 has no effect in old rats, and does not main- 

 tain spermatogenesis or the accessories in 

 hypophysectomized rats. Baker, Schairer, 

 Ingle and Li (1950) reported a small reduc- 

 tion in testicular weight in adult rats, but 

 spermatogenesis j^roceeded satisfactorily. 

 Large doses of ACTH produced atrophy of 

 the Leydig cells. Asling, Reinhardt and Li 

 (1951) stated that large doses depress the 

 weight of the accessory sex organs. How- 

 ever, Moore (1953) found that administra- 

 tion of 5 mg. ACTH per day for 10 days has 

 no effect on the testis of young or old rats 

 and has no extratesticular effect on the pro- 

 duction of androgen. 



D. MLSCELLAXEOU.S .STEROIDS AND MIXTURES 

 OF STEROIDS 



Masson (1945, 1946) studied 16 different 

 steroids for their ability to maintain sper- 

 matogenesis. Androstenediol, methylandro- 

 stenediol, methylandrostanediol, A'^-preg- 

 neninolone, and dehydroisoandrosterone are 

 the most active compounds in maintaining 

 spermatogenesis after hypophysectomy. No 

 relationship is apparent between the ability 

 to maintain spermatogenesis and the andro- 

 genic activity of the compound as measured 

 by stimulation of the seminal vesicles or the 

 progestational activity (progesterone is ef- 

 fective in maintenance but ethinyl testos- 

 terone is not). 



One compound, A^-pregneninolone, was 

 studied in detail. It prevents testicular atro- 

 phy after hypophysectomy or following 

 therapy with estradiol or testosterone; it 

 does not produce atrophy of the Leydig 

 cells. In doses of 1 to 2 mg. a day, preg- 



neninolone maintains spermatogenesis in 

 young and adult hypophysectomized rats, 

 l)ut it does not repair the tubules or Leydig 

 cells after a 2-week delay between hypoph- 

 ysectomy and therapy. Pregneninolone 

 also exerts a protective effect against the 

 damage evoked by estradiol; however, it 

 does not affect the regeneration that occurs 

 after cessation of estradiol treatment. In 

 this respect, it is different from testosterone, 

 which hastens the recovery from the estra- 

 diol-induced damage. In fact, the accelera- 

 tion of regeneration by testosterone is in- 

 hibited by pregneninolone. The chief 

 difference between pregneninolone-proges- 

 terone and testosterone-androstenediol is 

 that, whereas spermatogenesis is maintained 

 by either pair after hypophysectomy, the 

 former pair cannot restore spermatogenesis, 

 and the latter can. ]\Iost of these effects of 

 pregneninolone were confirmed by Dvoskin 

 (1949). Progesterone and some new proges- 

 tational compounds have been studied re- 

 cently in man (Heller, Laidlaw, Harvey and 

 Nelson, 1958). Progesterone given to normal 

 men produces azoospermia and slight tu- 

 bular atrophy, abolishes libido, and reduces 

 potentia, but has no effect on the Leydig 

 cells and the excretion of gonadotrophin, 

 estrogen, and 17-ketosteroids. 



Certain doses of desoxycorticosterone or 

 estradiol have no effect on the testis singly, 

 l)ut when mixed produce severe depression 

 of testicular weight (.lost and Libman, 

 1952). The earlier work of Emmens and 

 Parkes (1938), showing that testosterone 

 inhibits the debilitating action of estrone, 

 was confirmed by Joel (1942, 1945). The 

 testes of animals treated with estradiol are 

 one-sixth normal size; however, when tes- 

 tosterone propionate is added to the estro- 

 gen, the testicular weight is one-fourth nor- 

 mal. Furthermore, sperm cells are present 

 in the epididymides of the group receiving 

 testosterone. Mixtures of small amounts of 

 androstenediol and estradiol in a constant 

 proportion produce more profound atrophy 

 than large doses given in the same constant 

 proportion (Selye and Albert, 1942a, b; 

 Selye, 1943). Furthermore, androstenediol 

 and pregneninolone prevent the atrophy in- 

 duced by small doses of testosterone. Plence, 

 this protective action is not related to tes- 

 toid activity, because the first compound is 



