Endocrine Mechanisms 727 



Furthermore, at least in man and some dogs, an excess of pituitary sub- 

 stance after closure of the epiphyses results in the characteristic bone de- 

 formities of acromegaly. Skeletal abnormalities in the skull are also ob- 

 served in extract-treated or hypophysectomized mammals of other species. 



There is also clear evidence that crude alkaline pituitary extracts exert a 

 strong influence on growth of the soft tissues of the body. Protein metabolism 

 is affected in such a way as to increase the ratio of protein synthesis to pro- 

 tein degradation. A number of investigators have observed a significant drop 

 in blood non-protein nitrogen (N.P.N. ), urea, and amino acids, and a sub- 

 stantial drop in urinary N.P.N, after the injection. Mice injected with an- 

 terior lobe extract daily for 105 days have been shown to have increased 

 water, ash, and protein content. Fat content, on the other hand, may even 

 be reduced below that of controls. Thus the growth induced by the extract 

 resembles closely the growth observed in normal young and rapidly grow- 

 ing mammals. These changes can also be shown to occur in fasting as well 

 as in well-fed animals. These influences of the pituitary on growth are ex- 

 erted both through its known influences on other growth-essential endocrine 

 glands, such as the adrenals, thyroid, pancreas, and testes, and directly 

 through the action of a growth hormone arising in the pituitary itself. 



The problem of resolving the role of a growth-promoting principle from 

 the pituitary in the face of the numerous trophic influences of this origin 

 on other glands is a difficult one. Anterior lobe extract has been shown to 

 modify protein metabolism, as indicated by the striking drop in N.P.N, of 

 blood even after adrenalectomy, thyroidectomy, or pancreatectomy, although 

 after pancreatectomy the mammal must receive a standard insulin treatment 

 in order to obtain the N.P.N.-reducing action in response to the pituitary 

 extracts. These facts indicate that the action of the pituitary principle in ac- 

 celerating protein synthesis is exerted directly in the body rather than through 

 activities of other endocrines. 



The thyroid gland is essential to growth. Growth virtually ceases after 

 thyroidectomy in the young mammal, a dwarfed condition resulting. Admin- 

 istration of thyroxin to a thyroidectomized rat will restore normal growth. 

 If hypophysectomy has also been performed, the thyroid extract shows no 

 growth-promoting action. In such thyroidectomized and hypophysectomized 

 animals, anterior lobe extract alone will promote growth, but its action is 

 greatly increased by addition of thyroid hormone. In new-born rats, unlike 

 in older ones, thyroidectomy is followed by a failure of response to the pitui- 

 tary growth hormone. This appears to suggest that thyroxin is essential for 

 some developmental processes which must be completed before the capacity 

 to respond directly to the pituitary is present. 



Removal of the adrenal cortex of the mammal leads in a relatively short 

 time to death of the organism. Failure to grow is therefore obviously one of 

 the less significant accompaniments of adrenalectomy. Growth is restored 

 in adrenalectomized animals by administration of cortical .extracts; after both 

 adrenalectomy and hypophysectomy the growth response to anterior lobe ex- 

 tract is greatly enhanced by simultaneous administration of cortical extracts. 



Growth ceases or is greatly retarded in the absence of, or in deficiency of, 

 insulin from the islets within the pancreas. This hormone exerts qualitatively 

 the same type of action on blood N.P.N, as does the anterior lobe growth 



