MAMMALIAN TESTIS 



351 



This association indicates that estrogen is 

 involved in the formation of the tumor; in- 

 deed, it is chiefly by the use of estrogen that 

 experimental tumors in mice have been pro- 

 voked. 



Various natural and synthetic estrogens 

 are effective. For example, Hooker, Gardner 

 and Pfeiffer (1940) and Hooker and Pfeiffer 

 (1942) using estradiol and stilbestrol have 

 been able to produce interstitial cell tu- 

 mors in the A and C strains of mice, with 

 an incidence of 50 and 90 per cent respec- 

 tively. Treatment for 8 months with 16.6 to 

 50 fjig. of estradiol dibenzoate or 0.25 /xg. 

 stilbestrol weekly produces tumors, some of 

 which metastasize to the renal, lumbar, and 

 mediastinal lymph nodes. These tumors are 

 transplantable if the hosts are given estro- 

 gen. They are inhibited by the simultaneous 

 injection of testosterone. Tumors also may 

 be induced by implantation of pellets of 

 stilbestrol and cholesterol. The implantation 

 of a 4- to 6-mg. pellet of 10 to 25 per cent 

 stilbestrol in cholesterol induced tumors 

 within 5 months (Shimkin, Grady and An- 

 dervont, 1941). Of the various natural and 

 synthetic estrogens the triphenylethylene 

 derivatives appear to be the most potent. 

 Bonser (1942) and Gardner (1943) pro- 

 duced transplantable tumors in the JK, the 

 A, and the C 3H strains by triphenyl- 

 ethylene. Tumors thus induced are gen- 

 erally composed of interstitial cells. They 

 are transplantable only in the same strain 

 of mice and only when the hosts are given 

 estrogen. After several generations, how- 

 ever, the tumor may be transplanted with- 

 out administration of estrogen in normal 

 and in hypophysectomized mice (Gardner, 

 1945; Andervont, Shimkin and Canter, 

 1957). 



The tumors arise from hyperplastic inter- 

 stitial cells. The Leydig cells enlarge, be- 

 come foamy, and degenerate. JMacrophages 

 or, at least, cells containing a brown pig- 

 ment appear and phagocytose the exhausted 

 Leydig cells. A new crop of interstitial cells 

 appears from the mesenchyme. These may 

 grow faster in one zone than in another. The 

 faster-growing Leydig cells thus constitute 

 a nodule. The Leydig cells in the nodule also 

 become hyperplastic and foamy. These nod- 

 ules appear as white spots and cause pres- 

 sure atrophy of the tubules. Leydig cells in 



the tumor thus result from three genera- 

 tions, since the second crop of Leydig cells 

 is followed by a third generation containing 

 small primitive and hyperchromatic cells. 

 These contain brown pigment and hence 

 give the brown color to the tumor. At this 

 stage, the tumor may become necrotic, may 

 metastasize by way of lymph or blood, or 

 may invade locally. Such tumors secrete 

 both estrogen and androgen. The consensus 

 is that estrogen induces interstitial cell tu- 

 mors in mice by liberation of LH (Gardner, 

 1953). 



The assumption that LH induces inter- 

 stitial cell hyperplasia and finally a tumor 

 has received support from studies by Simp- 

 son and van Wagenen (1954) on young 

 monkeys. These investigators gave ICSH for 

 53 days. Hyperplasia of the Leydig cells 

 took place and nodules resulted. These nod- 

 ules were composed of concentric laminated 

 peritubular cells and arose from the same 

 type of mesenchymal cell that yields the 

 Leydig cell under normal conditions. Under 

 the influence of HCG, the nodules secreted 

 androgen. 



XVII. Conclusion 



The postnatal development of the mam- 

 malian testis follows a fairly definite pat- 

 tern. Development is slow for the variable 

 period of prepubertal life. The testis then 

 undergoes rapid evolution during puberty, 

 remains fairly constant in adult life, then 

 regresses somewhat in old age. The rapid de- 

 velopment of the testis during puberty is 

 brought about by the onset of gonadotrophic 

 function of the pituitary. This develop- 

 mental pattern is fixed for each species, but 

 can be modified by genie and environmental 

 factors. Once the adult status is attained, 

 secretory controls of androgenic and sper- 

 matogenic functions are established. A 

 steady state of testicular function is main- 

 tained in continuously breeding species. In 

 those mammals which show a seasonal 

 breeding cycle, these secretory controls, par- 

 ticularly those of the pituitary gland, are 

 periodically activated and deactivated. 



The testes of many eutherian mammals 

 migrate from the abdomen during fetal life 

 to the scrotum. This migration is regulated 

 by hormones of the fetus, presumably aris- 

 ing from the fetal testis. It is not clear just 



