STEROIDS AND GROWTH 387 



in males, as compared to females, after puberty is attributed to added 

 output from the testis. The titer of urinary androgens, measured bio- 

 logically, has also been determined in relationship to age by a number 

 of investigators (cf. Dorfman and Shipley, 1956). Such a bioassay is 

 not simple; it measures the effect of a complex mixture of steroids, con- 

 sisting of metabolic end products of different androgenic potencies 

 from multiple hormone precursors. However, such excretion data do 

 confirm the general statements made in regard to ketosteroid excretion. 



It is evident from the above that the increase in output of andro- 

 genic steroids that occurs during adolescence, as shown by increased 

 androgen and 17-ketosteroid excretion, is associated with the increase 

 in growth rate that take place at this time. Further evidence for the 

 role of androgens in the growth process may be noted from the fact 

 that testosterone can stimulate growth even when the pituitary is 

 deficient. It seems quite probable, therefore, that the adolescent spurt 

 in growth is due, at least in males, to androgens. Androgen secretion 

 also increases in the female during adolescence, and probably it ac- 

 counts for some of the increase in growth. The picture in girls is com- 

 plicated, as will be seen later, by the 'increased production of estrogen 

 that also occurs at this time and influences the growth process. 



Growth and epiphyseal cartilage. Linear growth finally ceases 

 when the epiphyses fuse to the long bones. Although the exact cause of 

 this fusion is not known, the androgens have been observed to be less 

 effective than estrogens in promoting epiphyseal fusion. It is thought 

 that androgens may influence this process either (a) by direct action 

 on the epiphyseal cartilage or (b) by inhibiting the secretion of growth 

 hormone. 



Before reviewing the available data on androgens and epiphyseal 

 cartilage, it is pertinent to review briefly the main effect of hypophy- 

 sectomy and growth hormone on this process. Hypophysectomy in the 

 rat and other species markedly arrests growth. The injection of purified 

 growth hormone (a protein) into hypophysectomized rats causes re- 

 sumption of growth, and if treatment is prolonged, the animals will 

 reach giant size [cf. Asling et al., 1955). A similar stimulation of 

 growth can be obtained by the administration of this hormone to nor- 

 mal young rats. The reactions of epiphyseal cartilage are important in 

 this growth response. Hypophysectomy arrests chondrogenic and osteo- 

 genic processes in the epiphyseal cartilages, producing a typical de- 

 crease in the width of the epiphyseal cartilage. The injection of growth 

 hormone stimulates the cartilages so that in width and histological ap- 

 pearance they resemble cartilage of young, normal, growing rats (cf. 

 Geschwind and Li, 1955 ) . 



Androgens and epiphyseal cartilage. Reports on the effect of testos- 

 terone on the epiphyses of the hypophysectomized rat vary consider- 



