270 



HYPOPHYSIS AND GONADOTROPHIC HORMONES 



than in gonadectomized animals of the 

 same sex. 



Intact adult female rats treated with tes- 

 tosterone show cessation of cycles (Nelson 

 and Merckel, 1937b), involution of the 

 corpora lutea, and a marked reduction in 

 ovarian weight (Greep and Chester Jones, 

 1950b j. The minimal effective inhibitory 

 dose is 10 /tg. daily. A dosage 50 times 

 greater (0.5 mg.j, however, does not pro- 

 duce the same severe degree of ovarian 

 atrophy that is seen with long-term estrogen 

 treatment. The ovaries, although small, have 

 a translucent blistery appearance. This is 

 due to the presence of a small number of 

 semi-atrophic vesicular follicles and to the 

 relatively great reduction in amount of 

 ovarian lipids (Greep and Chester Jones, 

 1950). From the foregoing evidence it would 

 appear that androgen treatment favors 

 FSH storage over FSH release and that 

 androgen can suppress both the elaboration 

 and I'elease of LH. 



The effect of exogenous androgens on the 

 gonads of the intact male rat varies widely 

 with the dose administered. Low to mod- 

 erate doses of testosterone produced severe 

 testicular injury (Selye and Friedman, 

 1941 ; Shay, Gershon-Cohen, Paschkis and 

 Fels, 1941; Rubinstein and Kurland, 1941; 

 Ludwig, 1950; Greep and Chester Jones, 

 1950b) ; maximal reduction in testes weight 

 and complete inhibition of spermatogenesis 

 were obtained with 0.1 mg. of testosterone 

 propionate daily for 30 to 45 days. Large 

 doses of androgen (2 to 20 mg. daily) main- 

 tained testis size and sperm production even 

 in the absence of the hypophysis (Walsh, 

 Cuyler and McCullagh, 1934; Cutuly, Mc- 

 Cullagh and Cutuly, 1937; Nelson, 1937; 

 Leathem, 1944) . The response is produced 

 by direct action on the tubular epithelium 

 of the testes. A similar effect was produced 

 in hypophyscctomized mice (Nelson and 

 Merckel, 1938), ral)bits (Greep, 1939), and 

 monkeys (P. E. Smith, 1944). Local mainte- 

 nance of spermatogenesis has also been ob- 

 served in the tubules in close proximity to 

 intratesticular implants of testosterone pel- 

 lets in hypopliysectomized rats (Dvoskin. 

 1947) and monkeys (P. E. Smith, 1944 ». 

 Several androgenic steroids and their deriva- 

 tives have been tested in regard to their 

 ability to maintain the testes in hypopliy- 



sectomized rats (Nelson, 1937). It is of in- 

 terest that the spermatogenic properties of 

 the various androgens were not found to be 

 related to their androgenicity as measured 

 by ability of the compounds to stimulate 

 the rat prostate or the capon's comb. Preg- 

 nenolone, a nonandrogenic steroid, did not 

 reinitiate spermatogenesis, but it did partly 

 maintain spermatogenesis, when given im- 

 mediately after hypophysectomy (Dvoskin, 

 1949). 



In man the testes apparently are not bene- 

 fited by exogenous androgens at any dose 

 level but are, on the contrary, affected ad- 

 versely. In 1940 Heckel noted a drop in 

 sperm count during testosterone therapy, a 

 finding that is now a common clinical ex- 

 perience. In the past few years much interest 

 has centered on the recovery phase. Heller, 

 Nelson, Hill, Henderson, Maddock, Jungck, 

 Paulsen and Mortimore ( 1950 », Heller, Nel- 

 son, Maddock, Jungck, Paulsen and Morti- 

 more (1951 ), and Ewell, Munson and Salter 

 (1950) reported finding a rebound in sper- 

 matogenesis and in sperm counts following 

 the cessation of androgen therapy. They ob- 

 served that for a year or more following 

 cessation of treatment the sperm counts 

 may be well above the pretreatment levels 

 and that scleroses and hyalinization of the 

 tubular walls may be lessened. The number 

 of cases studied has been extended (Heckel, 

 Rosso and Kestel, 1951; Heckel and ]Mc- 

 Donald, 1952; Swyer, 1956) with poor 

 agreement as to improvement in sperm 

 count. Because the already subnormal testis 

 is further damaged by androgen, there is 

 need for additional study of this interesting 

 phenomenon. 



Although rats and man have been ex- 

 tensively investigated, little information is 

 available about other mammals. Wells 

 (1943) injected male ground squirrels with 

 testosterone in daily doses from 0.05 to 20 

 mg. beginning just before the peak of the 

 annual sexual cycle. He found that the in- 

 terstitial cells were severely damaged and 

 the testes were somewhat reduced in size, 

 but the spermatogenic capacity of tubular 

 einthelium was unimpaired. His assump- 

 tion that the release of ICSH was being 

 inhibited has been amply substantiated by 

 other studies. His failure to find tubular 

 ati'()i)hv with the low doses is I'atlu'i' sur- 



