346 E. ROBERTS AND D. G. SIMONSEN 
and the behavioral development is retarded (see ref. 77 for summary). In all cases, 
the chromatographic patterns of the brain tissue of the control and experimental 
animals were indistinguishable. 
Thus, although profound effects are produced by thyroxin excess or deficiency in 
animals at virtually all levels of observation only minimal changes are produced 
in the free amino acids of the tissues which have been studied. 
Hypophysectomy and adrenalectomy. Sprague-Dawley rats either were hypophy- 
sectomized or adrenalectomized at 40 days of age. The hypophysectomized rats and 
unoperated littermates were sacrificed at 12 days after surgery, the operated animals 
weighing 30-50% less than the controls. The bilaterally adrenalectomized rats were 
sacrificed at 6 and 11 days and weighed 10-30% less than the normal controls. 
Typical results for liver, kidney, muscle and brain are shown in Figs. 327-338. The 
variations in taurine content in the livers were no greater than those observed from 
one control to another. There was an increase in content of ethanolamine phosphate 
in kidneys and livers of hypophysectomized animals, as was the case for thyroidecto- 
mized animals. Virtually no other significant changes were seen in the amino acid 
patterns of the tissues of the experimental animals. The results obtained in these 
groups of animals are in keeping with the previously observed stability of the steady- 
state concentrations of the free amino acids in tissues of animals subjected to various 
physiological stresses. 
DISCUSSION 
The relative constancy of the concentrations of easily extractable ninhydrin-reactive 
constituents found in the tissues of mature animals under a variety of physiological 
conditions suggests that the concentrations of these substances are regulated by 
remarkable biological servo-mechanisms which involve not only the coordination of 
the rates of a variety of complex biosynthetic and degradative pathways but also 
the continuous adjustment of the rates of entry into cells and exit from cells and the 
movements between intracellular sites and organelles. The characteristic amino acid 
patterns are largely maintained in the tissues when changes take place in the external 
environment of the animal. This was illustrated in the present report primarily in 
the discussion of experiments in which it was found that only small changes in tissue 
amino acids were produced by starvation, dehydration, or potassium or vitamin A 
deficiencies. The characteristic distribution of the amino acids and related sub- 
stances were retained by the tissues of organisms even when major disturbances 
were produced in the homeostatic mechanisms of the animal as a whole. Thus, 
thyroxin injection, thyroidectomy, hypophysectomy, adrenalectomy, production of 
diabetes and the induction of progressive, eventually fatal growth of tumors pro- 
duced only small changes in the free amino acid patterns of liver, kidney, muscle 
and brain. A number of the above experimental alterations is known to be accom- 
panied by some significant changes in enzyme activities and in content of various 
proteins, nucleic acids, lipids and polysaccharides in at least some of the tissues 
studied. Therefore, the constancy of the amounts of the small molecular weight 
substances with which we have been concerned may be maintained even when some 
changes take place in the macromolecular composition of the intracellular environ- 
ment. Nor do the patterns of amino acids appear to depend on intactness of micro- 
References p. 348/349 
