338 



PHYSIOLOGY OF GONADS 



cept of a servomechanism controlling pitui- 

 tary-testis activities was well established. 

 According to this concept, male hormone 

 was considered to have its major effect on 

 the testis by inhibiting the secretion of pi- 

 tuitary gonadotrophins. However, it was 

 difficult to fit into this concept the report 

 by Walsh, Cuyler and McCullagh (1934) 

 that testosterone was capable of maintain- 

 ing spermatogenesis in the rat after hypoph- 

 ysectomy. If testosterone were the medium 

 by which spermatogenesis was maintained 

 normally, the dualistic concept of gonado- 

 trophic control of the testis would be in 

 jeopardy. As can be imagined, this finding 

 stimulated much research. By 1940 the fact 

 that spermatogenesis is maintained in hy- 

 pophysectomized rats, mice, and rabbits by 

 testosterone was amply established (Cutuly 

 and Cutuly, 1940) . 



A. ANDROGENS 



The varied effects obtained by injecting 

 male hormone into normal and hypophysec- 

 tomized rats depend on the nature of the 

 androgen, the dose, the length of the treat- 

 ment period, and the age of the animals 

 when injections are begun. Inasmuch as 

 most of the experimental work has been 

 done with the rat and rats of various ages 

 and sizes were employed, it is obvious that 

 the dose of hormone is an important factor. 

 Doses of testosterone of 100 /xg. per day or 

 less can be regarded as small doses, whereas 

 doses of 1 mg. or more can be considered as 

 large. These definitions pertain only to the 

 doses employed in studying the action of 

 androgen on the testis and do not neces- 

 sarily have any relationship to the physio- 

 logic levels of testosterone produced by the 

 rat testis, which is not known, or to the 

 effects of testosterone on the accessory sex 

 organs (Moore, 1939). 



In general, testosterone has no action on 

 the undifferentiated gonad of the mouse, rat, 

 opossum, or guinea pig (Moore and Morgan, 

 1942). In the immature rat small doses of 

 testosterone propionate depress the testicu- 

 lar weight (Zahler, 1947; Dischreit, 1939; 

 Greene and Burrill, 1940). However, if 

 small doses are continued for long periods, 

 incomplete supi:)ression results. Because the 

 testicular inhil^ition induced by small doses 

 of testosterone apparently results from sup- 



pression of gonadotrophins, it seems that 

 greater ciuantities of gonadotrophins are 

 formed as rats grow; hence, escape from 

 suppression may occur (Biddulph, 1939). 

 The work of Rubinstein and Kurland (1941) 

 indicates that even small doses of testos- 

 terone, as already defined, may produce 

 dift'erent effects in the rat. These investi- 

 gators compared the effects of administra- 

 tion of 5 and 50 fxg. testosterone propionate 

 per day in young animals. Young rats re- 

 ceiving the former dose showed increased 

 testicular weight without, however, any 

 hastening of maturation of sperm cells. The 

 larger dose decreased testicular weight. 



The effect of androgen on mature rats is 

 also dependent on dose. Small doses cause 

 atrophy of the mature testis because of 

 suppression of gonadotrophins. Large doses 

 have the same suppressing effect, but this 

 is overridden by a direct stimulating effect 

 of androgen on the testis, and atrophy does 

 not occur. In both instances, the Leydig 

 cells are atrophic (Shay, Gershon-Cohen, 

 Paschkis and Fels, 1941). Large doses of 

 testosterone have a direct action on the 

 testis as indicated by the protective effect 

 exerted on the experimentally induced 

 cryptorchid testis (Hamilton and Leonard, 

 1938) and on the transplanted testis (Klein 

 and Mayer, 1942) . 



The aftereffects of androgenic adminis- 

 tration also depend on the age of the animal 

 and the duration of therapy. Using fecun- 

 dity, libido, potency, and the state of the 

 reproductive tract as indices of testicular 

 function, Wilson and Wilson (1943) ex- 

 amined rats 3 to 5 months after a 28-day 

 period of injection of androgen. In rats age 

 1 to 28 days, androgen severely affected the 

 reproductive system. Low libido, absence of 

 fecundity, and atrophic accessories were 

 noted 3 to 5 months after testosterone ther- 

 apy was discontinued. However, the later 

 this treatment was instituted in the life of 

 the rat, the more normal was the repro- 

 ductive system 3 to 5 months after adminis- 

 tration of the hormone was stopped. 



Nelson and Merckel (1937), in a series of 

 extensive experiments, confirmed the earlier 

 finding that various androgens maintain 

 spermatogenesis in the rat after hypophy- 

 sectomy. Furthermore, they showed that the 

 Leydig cells are atroj^hic in the face of 



