342 



PHYSIOLOGY OF GONADS 



paired morphologically, to secrete androgen 

 which by virtue of its local action on the 

 tubules maintained spermatogenesis (Lud- 

 wig, 1950). 



Testosterone maintains spermatogenesis 

 in other species. In hypophysectomized 

 ground squirrels, the testes are atrophic, 

 aspermatic, and abdominal (Wells, 1942; 

 1943a). Hypophysectomized animals given 

 testosterone propionate (0.5 mg. per day for 

 15 to 25 days) show growth of the testes, 

 sperm formation, and testicular descent. 

 Leydig cells remain atrophic. Because sperm 

 formation ceases after hypophysectomy in 

 the ground squirrel, as it does in the mon- 

 key, rat, guinea pig, mouse, cat, and ferret, 



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»^--r- 



Fic. .').21. KIT(H't of .iihlhitiMi HI ,( liypophysocto- 

 mized inoiikoj-. 1, biop-x -iniiincn from a normal 

 8-kg. rhesus monkey. .'. liiii|i-\ specimen from a 

 hypophysectomized monkey .ifici- 56 da.ys, during 

 which 1.4 gm. of testosterone propionate was ad- 

 ministered at a daily dose of 25 mg. 3, state of 

 testis 20 days after use of testosterone was dis- 

 continued. Note atrophy of tubules. The Sertoli 

 cells and spermatogonia remain. (From P. E. 

 Smith, Yale J. Biol. & Me.l., 17, 281, 1944.) 



it is obvious that androgen initiated sperma- 

 togenesis. 



Testosterone propionate maintains the 

 spermatogenic activity of the testis of the 

 hypophysectomized monkey for 20 to 50 

 days (van Wagenen and Simpson, 1954). A 

 dose of about 20 mg. per day is required. 

 When medication is discontinued, marked 

 involution of the testis occurs within the 

 ensuing 3 weeks. Testosterone is effective 

 even after a lapse of 50 days between hy- 

 pophysectomy and the institution of ther- 

 apy. Spermatogenesis can be restored and 

 formation of motile sperm cells induced. As 

 in the rat, the testes maintained by androgen 

 are smaller than normal. Pellets of testoster- 

 one implanted locally exert a strong local ac- 

 tion. Thus, the essential findings in the rat 

 are duplicated in the monkey (Fig. 5.21). 



In man the effects of testosterone on the 

 testis have been studied by Hotchkiss 

 (1944a), and by Heller, Nelson, Hill, Hen- 

 derson, Maddock, Jungck, Paulsen and Mor- 

 timore (1950). The main effects were dis- 

 appearance of the Leydig cells, atrophy of 

 the tubules, arrest of spermatogenesis, and 

 pronounced hyalinization of the basement 

 membrane (Fig. 5.22). Complete recovery 

 of the testis occurred 17 months after cessa- 

 tion of therapy. In fact, the testes were 

 histologically more normal than before 

 treatment. The improvement in sperm pro- 

 duction after preliminary depression of the 

 testis by administration of testosterone has 

 been used widely in the treatment of male 

 infertility. Heckel, Rosso and Kestel (1951) 

 and Heckel and McDonald (1952a, b) ob- 

 tained an increase in spermatogenic activ- 

 ity, as determined by sperm counts and 

 biopsy, after cessation of treatment. This 

 increase was termed a "rebound phenome- 

 non"; during it, increased fertility, as de- 

 termined by an increased incidence of preg- 

 nancy among infertile couples, was reported. 

 The improved quality and quantity of 

 sperm following therai)y with testosterone 

 are transient. Furthermore, they occur in 

 only a small i^-oportion of men so treated 

 (Getzoff, 1955; Heinke and Tonutti, 1956). 

 The suppressive effect of androgen on the 

 human testis results from inhibition of pitui- 

 tary gonadotrophin as evidenced by meas- 

 urement of the amount of urinary gonado- 

 trophin before, during, and after use of 



