356 CELLS, TISSUES, AND ORGANISMS 



function were often observed when the experimental giants came to 

 autopsy, but subsequent fractionation of the pituitary extract yielded 

 preparations which were able to stimulate the growth of normal and 

 hypophysectomized rats without producing other notable effects. In 

 succeeding years, concerted efforts to isolate, purify, and characterize 

 the active growth-promoting principle of the adenohypophysis culmi- 

 nated in the preparation of highly purified, crystalline protein fractions 

 (Li et al, 1945; Wilhelmi et al., 1948). These had virtually no activity 

 in stimulating the adrenals, thyroid, or gonads, but they nevertheless 

 exhibited the growth-promoting properties of cruder extracts when in- 

 jected into normal or hypophysectomized rats. For lack of a better 

 term, this material has been called "growth hormone," but the more 

 sophisticated appellations of "somatotropic hormone" (STH) or "so- 

 matotropin" are gaining in favor. 



The administration of small quantities of growth hormone for pro- 

 longed periods of time to normal and hypophysectomized rats results 

 in a striking increase in body weight and size (Evans, et al., 1948; 

 Simpson et al., 1949). The skeleton undergoes changes characterized 

 by an elongation and widening of the long bones (Simpson et al., 

 1950) and enlargement of the skull. This increase in skeletal dimen- 

 sions is accompanied by an increase in the weight and size of the non- 

 endocrine viscera and a marked hypertrophy of the musculature, skin, 

 connective tissues, and lymphoid tissues (see Ketterer, Randle, and 

 Young, 1957, for review). These effects, while modified by the thyroid, 

 adrenals, and gonads, can nevertheless be observed in their absence 

 (see Simpson et al., 1950), thus strengthening the view that growth 

 hormone has a direct action on the tissues it influences. 



Curiously, the growth of the central nervous system and its deriva- 

 tives seems to be relatively independent of the action of growth hor- 

 mone, since they fail to grow at an accelerated rate when the hormone 

 is administered (Simpson et al., 1949) and continue to grow in very 

 young animals that have been hypophysectomized. The latter situation 

 may lead to lethal brain damage, due to the compression of the grow- 

 ing brain by the cranium, which has ceased to expand (Asling et al., 

 1952). As noted above, the reproductive organs, as well as the adrenal 

 and thyroid glands, are similarly unaffected by growth hormone in the 

 absence of other, more specific hormonal stimuli. 



The body composition of animals treated with growth hormone, 

 when compared with that of their pair-fed controls, characteristically 

 reveals an increase in the proportion of protein and water and a reduc- 

 tion in the proportion of fat (Li and Evans, 1948) with a resultant 

 carcass composition resembling that seen in very young animals. There 

 can be no doubt that the accretion in body size occasioned by the ad- 

 ministration of the hormone is indeed due to the synthesis of new tissue 



