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As previously reported, an increased concentration of plasma free amino acids, particularly lysine and threonine, was found when chicks were fasted for 24 hours. This increase was suppressed where a nonprotein diet was fed. Dextrose as the chief energy source in the nonprotein diet was more effective than shortening or lard in this respect. However, the degree to which the two energy sources differed was less where birds were adapted to the utilization of fat by feeding a diet rich in fat for a considerable time before making the comparison. Insulin administration to fasted chicks was found to lower plasma amino acid levels. The possible influence of interrelationships among dextrose, fat, and insulin on plasma amino acid levels is discussed.

In rat ventral prostate the action of many natural androgens, including testosterone, appears to depend on their conversion to 5α-dihydrotestosterone that binds firmly to an androgen receptor (β protein) and is subsequently retained by cell nuclei. We have found, however, that many potent synthetic androgens can bind directly to β protein and to prostate cell nuclei without a metabolic conversion. For these studies, simple methods were devised to compare the receptor binding affinities of various androgenic steroids. These methods are especially useful if test compounds are available only in minute quantities (l1 µg). In general, the correlation between the relative competition indices of various synthetic androgens determined by these procedures and the relative androgenicities of these androgens was very good. This supports the concept that the β protein and nuclear binding of androgens play important roles in androgen actions in ventral prostates. Most of the highly active synthetic androgens that could bind to β protein were Δ4-3-ketosteroids without an angular methyl group at C-10. Since they can bind to β protein tightly, their androgen action may bypass the action of Δ4-3-ketosteroid-5α-oxidoreductase that appears to be necessary for the action of testosterone. These findings, together with molecular model building, indicate that the bulkiness and flatness of the steroid molecule play a more important role in receptor binding than the detailed electronic structure at the Δ4 bond of Ring A. For example, potent androgens with conjugated double bonds extending from Rings A and B to C (such as 2-oxa-17α-methyl-17β-hydroxy-estra-4,9,11-triene-3-one and 17α-methyl-17β-hydroxy-estra-4,9,11-triene-3-one) are indeed very flat molecules and bind to the androgen receptor firmly. Substitution of a 7α-methyl group in 17β-hydroxyestr-4-en-3-one (19-nortestosterone) or its 17α-methyl derivative enhanced the androgenic activities of the parent compounds as well as their ability to bind to β protein and to prostate cell nuclei. Thus, 7α, 17α-dimethyl-19-nortestosterone had an apparent affinity for βprotein several times higher than that of 5α-dihydrotestosterone. A tritiated form of 7α, 17α-dimethyl-19-nortestosterone was also used to show its binding to β protein and to prostate cell nuclei. The tritiated androgen appeared to be very stable to metabolic conversion in prostate tissue. Notably, it was not reduced by prostate Δ4-3-ketosteroid-5α-oxidoreductase.

Inhibition of uptake of cationic amino acids by certain neutral amino acids in the presence of alkali metal ions has been studied in the Ehrlich ascites tumor cell, in the rabbit reticulocyte and in yeast. When a hydroxyl group is introduced on carbon 4 (for the reticulocyte) or carbon 5 (for the Ehrlich cell) of straight chain amino acids, a sharp shift in the selectivity among the alkali metal ions occurs in favor of Na+ or of Na+ and K+ in the two animal cells. This shift is associated with attainment of a maximal interaction between the neutral amino acid and the alkali metal, and is taken to support a bridging by the ion between the amino acid and the receptor site. Although in both potassium-treated and glucose-treated yeast neutral amino acids also become much more inhibitory to cationic amino acid uptake in the presence of alkali metal ions, no augmentation has been observed on introduction of a side chain hydroxyl group, and selectivity among the ions is weak. Hence a bridging function is doubted for that organism. The ions exert additional inhibitory effects, independent of the presence of a neutral amino acid, which appear to be competitive with H+.

IN A previous paper (Shao and Hill, 1968) it was reported that thiouracil as a dietary supplement reduced the concentration of free lysine, threonine, tryptophan, methionine and leucine in the blood plasma of chicks. The present paper gives the results of experiments in which thiouracil and/or iodinated casein were added to a basal diet and extends the observations to several additional amino acids. EXPERIMENTAL The basal diet, essentially a wheat, corn soybean meal mixture, was described in detail by Shao and Hill (1968). White Plymouth Rock pullets were fed this diet from day old to 7 days of age and then divided on the basis of weight into lots of 12 chicks each. The experimental diets were assigned to these lots at random, each diet to 4 lots and the experiments continued for another 14 to 15 days. Blood samples were removed from each chick in two lots per treatment…

LEVELS of free amino acids as determined in the blood plasma of chicks can be quite variable even though the chicks are fed similar diets and are of the same breed, sex and age (Shao and Hill, 1967; Hill and Olsen, 1963). An unusually high level of lysine and threonine observed in an experiment in which blood was sampled under conditions of extremely high summer temperature (Hill and Olsen, 1965), prompted us to consider the possibility that the metabolic rate of the bird at the time of sampling might influence plasma amino acid levels. As a test of this hypothesis we measured the plasma amino acids following administration of thiouracil at a level which might be presumed to lower metabolic rate (Singh and Shaffner, 1950; McCartney and Shaffner, 1950, 1949; Shaffner and Andrews, 1948). Although the observations in the present paper did not support the above hypothesis they are believed . . .