602 



Ontogeny of Endocrine Correlation 



ministration to pituitaryless rats fails to 

 stimulate growth. Although these results in- 

 dicated that the anterior pituitary alone is 

 essential for body growth, it was early shown 

 by Smith ('33) that the hormones of both 

 glands have to some extent a synergistic 

 action in promoting growth. This was 

 brought out by the discovery that the simul- 

 taneous administration of growth-hormone 

 extracts and of thyroid (the latter in dosages 

 insufficient to prevent increase in weight) 

 to rats dwarfed by removal of both anterior 

 pituitary and thyroid during active postnatal 

 growth causes a significantly greater skeletal 

 growth and increase in body length and 

 weight than when growth hormone extracts 

 alone are given. 



This original concept of synergistic action 

 has been confirmed and broadened by the 

 use of hormones in chemically purified form 

 as they became available. Purified growth 

 hormone restores growth in hypophysecto- 

 mized rats (also stimulates overgrowth in 

 normal animals), whereas thyroxine has 

 only an insignificant effect on increase in 

 body weight (Marx et al., '42). In combina- 

 tion these hormones are more effective in 

 promoting growth. Thyroxine augments the 

 purified growth hormone in increasing body 

 weight and in reactivating skeletal growth 

 in rats dwarfed by hypophysectomy at 26 to 

 30 days after birth. The increase in body 

 weight and length of animals, even after a 

 postoperative interval of one year or longer, 

 is significantly greater when both hormones 

 in optimal proportions to each other are 

 administered than when the growth hormone 

 alone is given (Evans, Simpson, and Pen- 

 charz, '39; Becks et al., '46). Similarly, the 

 capacity of the growth hormone to stimulate 

 growth in pituitaryless rats is markedly en- 

 hanced in combination with thyrotrophic 

 hormone preparations. The thyrotrophic 

 hormone seems to parallel thyroxine in its 

 synergistic effect with growth hormone in 

 promoting the growth of tissues. It seems 

 probable that the thyrotrophic hormone ex- 

 erts its effect indirectly by increasing the 

 activity of the thyroid gland, but this point 

 has apparently not been clarified. Beyond 

 the apparent stimulation of the synthesis 

 and retention of protein nothing is known 

 concerning the mechanism of the synergistic 

 action of these hormones. 



In contrast to thyroxine, partially purified 

 ACTH has a counteracting effect on the ac- 

 tion of the growth hormone. In female rats 

 hypophysectomized at 26 to 28 days of age, 

 ACTH in combination with the growth 



hormone almost completely nullifies the 

 growth-promoting action of the latter. There 

 is little or no gain in body weight or increase 

 in width of the epiphysis (tibia), as opposed 

 to a marked increase in these features ob- 

 tained with growth hormone alone. ACTH 

 alone is ineffective in eliciting an increase in 

 growth of the body or the epiphysis of the 

 tibia. However, the adrenal glands exhibit a 

 marked increase in weight under the in- 

 fluence of ACTH alone or in combination 

 with growth hormones (Evans et al., '43). 

 The fact that the adrenals are hypertrophied 

 (stimulated by ACTH) furnishes presump- 

 tive evidence that adrenal cortical hormones 

 are involved, especially since somatic growth 

 is apparently not inhibited by ACTH in rats 

 deprived of the adrenals and is retarded in 

 normal growing rats by the administration 

 of adrenal cortical hormones. 



How can these observations be interpreted 

 in terms of hormonal action on growth proc- 

 esses? On the basis of considerable evidence, 

 the most plausible interpretation is that 

 both the growth and the adrenal cortical 

 hormones alter metabolic processes but in 

 opposite directions. The growth hormone 

 seems to have the property of promoting pro- 

 tein synthesis and retention, and as a con- 

 sequence promotes bodily growth. The adre- 

 nal cortical hormones, on the other hand, 

 owing to their capacity to accelerate the 

 catabolic phases of protein metabolism, have 

 a retarding effect on rats. (For supporting 

 evidence and theory see Long, '42, '43, '49.) 



Thus, in rats at the stages of growth under 

 consideration there exists an interlocking of 

 function of the hormones of the anterior 

 pituitary and at least of the thyroid and 

 adrenal cortex in regulating the growth 

 processes. A disturbance in the quantity or 

 rate of hormonal output of any one of these 

 endocrine glands seems to produce a hor- 

 monal imbalance, the consequence of which 

 is an arrest, retardation, or distortion of the 

 growth processes. In the normal animal it 

 seems probable that the quantity or rate of 

 output of each of these hormones is regu- 

 lated by a delicate balance in hormonal 

 level in the blood stream, which in turn is 

 adjusted to the growth potential of the or- 

 ganism. Although this picture is relatively 

 simple and general, it must be recognized 

 that other hormones such as insulin are in- 

 volved in the unusual complexity of factors 

 that influence growth (see pp. 607-611). 



The question next arises as to whether the 

 interlocking of hormonal function operating 

 at 26 to 30 days in regulating growth is 



