STEROIDS AND GROWTH 395 



growth and musculature, and in 1895 Sacchi described the eflFects of a 

 tumor of this type in a nine and a half-year-old boy. In addition to 

 precocious arrival of puberty, the boy also had adult genitalia, a full 

 beard, and the musclature of a grown man. Adrenocortical tumors may 

 also put out larger amounts of androgen, producing the so-called in- 

 fant Hercules syndrome. Similar changes may be noted in the female 

 with bilateral hyperplastic adrenal cortices. The active adrenal tissue 

 in such patients produces an excess of androgenic compounds, result- 

 ing in hypertrophy of the clitoris, masculine hirsutism, acne, rapid 

 growth, and heavy musculature. 



These observations indicated that testicular functions in general 

 are associated not only with the reproductive function but also with 

 anabolic activity. The term "anabolism" is defined as a constructive 

 metabolism, indicating the building or formation of tissues in general. 

 Thus, the typical androgenic steroids have anabolic as well as andro- 

 genic efiFects. Testosterone propionate, for example, can produce a 

 positive nitrogen balance and retention of phosphorus and potassium. 

 Retention of calcium also may occur, and it has been inferred from this 

 that further formation and/or calcification of bone occurs. 



Anabolic effect of testosterone. It was not until 1935 that Kocha- 

 kian and Murlin first demonstrated that an extract of human male urine 

 not only had androgenic eflfects but also caused nitrogen retention in 

 castrate dogs fed a constant diet. After this observation, testosterone 

 and testosterone acetate also were observed to produce nitrogen reten- 

 tion in the castrated dog ( Kochakian, 1937 ) . Since then these anabolic 

 eflFects have been amply confirmed in various studies on rats and dogs. 

 With regard to man, Kenyon and co-workers ( 1938 ) and others have 

 demonstrated that testosterone propionate will decrease the urinary- 

 nitrogen excretion both in eunuchoidal individuals and in subjects with 

 normally functioning gonads ( cf. Kochakian, 1946 ) . 



The nitrogen-retaining eflFects of testosterone are reflected in an 

 increased weight gain in both animals and man. Kochakian has studied 

 the growth rate of internal organs and 49 individual muscles of the 

 normal and castrate guinea pig, demonstrating that androgens increase 

 the size of many atrophied muscles {cf. Kochakian and Tillotson, 

 1956 ) . Attempts have been made to utilize the anabolic action of testos- 

 terone for underweight patients, in cachectic disease states, in oste- 

 oporosis, and in patients with hepatic cirrhosis. The androgenic side- 

 eflFects of testosterone have usually limited its use, the patients develop- 

 ing hirsutism, deepening of the voice, and other masculinizing changes. 

 Retention of sodium also may occur, particularly in patients with 

 hepatic disease. 



Nortestosterone derivatives. Certain steroids have been reported 

 to show a difference in the ratio of anabolic to androgenic effects. 



