350 



PHYSIOLOGY OF GONADS 



reconnaissance, attempt to mount their af- 

 flicted pets. In addition to the feminization, 

 evidence that Sertoli-cell tumors produce 

 estrogen comes from the finding of estrogen 

 in the urine of tumor-bearing animals and 

 from the extraction of estrogen from the 

 tumor itself (Berthrong, Goodwin and Scott, 

 1949). In terms of estradiol, the concentra- 

 tion of estrogen extracted from a Sertoli-cell 

 tumor (Huggins and Moulder, 1945) was 

 twice that found in the ovary from an es- 

 trous bitch. Sufficient estrogen appears to be 

 produced to cause such changes as loss of 

 hair, depression of libido, cystic hyperplasia 

 of the mammary glands, and atrophy of the 

 testis. 



Interstitial cell tumors in dogs are usu- 

 ally nonfunctional, but they may produce 

 estrogen (Laufer and Sulman, 1956; Kahan, 

 1955). Leydig-cell tumors have been re- 

 ported in the mule, the Brahma bull, and 

 the saddle horse (Smith, 1954). Signifi- 

 cantly, in the last instance, an interstitial 

 cell tumor occurred in the undescended tes- 

 tis of a 7-year-old horse, the descended tes- 

 tis having been removed early in life. 



In man the proportion of various types of 

 testicular tumors is different from that in 

 lower animals. Seminomas and embryonal 

 carcinomas are the most frequent neo- 

 plasms. Interstitial cell tumors have been 

 recorded in less than two dozen instances in 

 the world literature. Several cases of Ley- 

 dig-cell tumor have been studied by Ven- 

 ning (1942) , Cook, Gross, Landing and Zyg- 

 muntowicz (1952), Hertz, Cohen, Lewis and 

 Firminger (1953), and Jungck, Thrash, Ohl- 

 macher, Knight and Dyrenforth (1957). 

 This tumor causes isosexual precocity in 

 boys. Signs of androgenic activity are evi- 

 dent in the large penis ; scrotal maturation ; 

 the appearance of pubic, facial, and axillary 

 hair, and acne; increased bodily growth; 

 maturation of the larynx; and increased 

 excretion of 17-ketosteroids. All these find- 

 ings occur when sufficient amounts of 

 testosterone are injected into normal pre- 

 pubertal boys. This tumor cannot conceiva- 

 bly be related to the secretion of LH (see 

 subsequent material on experimental tu- 

 mors), because the neoplasms are usually 

 unilateral and the contralateral normal tes- 

 tis shows no activation of the Leydig cells. 



Neoplasms classified as Sertoli-cell tu- 



mors are rich in lipids and are thought to 

 secrete estrogen (Teilum, 1950). However, 

 the histogenesis of these tumors is not clear, 

 and there is doubt that Sertoli-cell tumors 

 actually occur in man. 



Testicular tumors have been induced in 

 rats by transplantation of immature testes 

 to the spleen of castrated adult animals 

 (Biskind and Biskind, 1945) and by radia- 

 tion, carcinogens, and other means (Peyron 

 and Samsonoff', 1941). Transplantation of 

 day-old rat testes to the spleen of castrated 

 adult rats, normal male rats, and castrated 

 adult female rats resulted in the formation 

 of encapsulated and sharply circumscribed 

 tumors. Of 29 tumors thus produced, 16 

 were composed entirely of interstitial cells 

 and 13 contained other testicular elements 

 as well. One of the tumors was transplant- 

 able into the spleen of a castrated animal. 

 Because hyperplasia of the interstitial cells 

 was seen in most of the transplanted testes, 

 it was thought that the neoplasia followed 

 the hyperplasia induced by the excess of 

 gonadotrophin in the castrated host 

 (Twombly, Meisel and Stout, 1949). Such 

 Leydig-cell tumors produce estrogen (Fels 

 and Bur, 1956). 



In contrast with the rat, experimental tu- 

 mors in the mouse are not induced by any 

 of the methods already mentioned (Gardner, 

 1953). Spontaneous tumors of the testis in 

 mice do occur, however. Slye, Holmes and 

 Wells (1919) found 28 testicular tumors in 

 some 9000 male mice. None formed meta- 

 static lesions. Hummel (1954) reported a 

 spontaneous tumor in an 18-month-old 

 mouse of the BALBC strain; this neoplasm 

 was transplantable for three generations in 

 normal or gonadectomized adult males or 

 females. This was a functioning tumor as 

 evidenced by masculinization of the sub- 

 maxillary glands, mucification of the vagina, 

 hypertrophy of the clitoris, and an increase 

 in size of the uterus of the female host and 

 of the accessory sex organs of the male host. 

 All these findings indicate estrogenic and 

 androgenic secretion. In general, however, 

 interstitial cell tumors in mice are strain- 

 limited, occurring particularly in the AC 

 and JK strains. Spontaneous interstitial cell 

 tumors also occur in hybrids and are as- 

 sociated with mammary tumors (Gardner, 

 Pfeiffcr, Trentin and Wolstenholme, 1953). 



