Kathleen Lugibihl

The effect of progesterone on the concentration of plasma amino acids in man

Abstract Progesterone is a catabolic hormone in man. In four subjects a progesterone induced catabolic process was accompanied by a prompt decline in the plasma concentrations of a number of free amino acids. Threonine, proline, glycine, alanine, lysine, arginine, ornithine, citrulline, cystine and serine concentrations were very significantly lowered. Valine, tyrosine, and histidine were significantly lower. The concentrations of methionine, isoleucine and leucine tended to move downward. Only the phenylalanine level was clearly uninfluenced. Previous studies had shown that total urinary amino acid nitrogen was unaffected by progesterone. Results in these experiments were corroborative in that urinary glycine, alanine, methionine and arginine were not influenced by treatment with progesterone. On the basis of these results it has been suggested that the catabolic action of progesterone is secondary to an enhancement of amino acid utilization by the liver, and that the circulating concentrations of one or several amino acids exert a negative feedback action on the rate at which amino acids are liberated from peripheral tissues. On the basis of the fact that during progesterone treatment only the concentrations of glycine, threonine, cystine and serine were lower fasting and postprandially than they were fasting on control days, it has been suggested that one of these four compounds, or a combination of several of them, may be critical in regulating peripheral protein catabolism.

Effect of glucagon on concentration of several free amino acids in plasma

Abstract The protein catabolic influence of glucagon is known to be accompanied by a significant drop in the total plasma free amino acid concentration. In these studies carried out on four subjects it has been shown that the plasma concentration of threonine, proline, glycine, alanine, lysine, arginine, citrulline, serine, cystine and histidine were very significantly lowered by catabolic doses of glucagon ( 3 4 -1 mg. every 6 hours ). The concentration of methionine, valine, and tyrosine were significantly lowered. The leucine level was probably significantly lower than control values. Only the phenylalamine concentration was not significantly affected in these studies. The effect was noted 30 minutes after injection of glucagon in one subject. Urinary amino acid nitrogen declined slightly. The pattern of the glucagon effect on amino acid concentrations was quite similar to that of progesterone which is also catabolic. In the glucagon studies, only the concentrations of glycine and cystine were so lowered that even following a high protein meal when plasma levels rise, they were as low or lower than fasting non-treatment levels. It is suggested that the catabolic effect of glucagon and progesterone is due primarily to an enhancement of hepatic utilization of amino acids, and that the resulting lowered plasma level of one or several amino acids enhances mobilization of more amino acids from peripheral tissues. On the basis of these studies and the plasma amino acid levels observed during catabolic processes induced by progesterone, thyroid and glucocorticoids, it is suggested that the glycine concentration in plasma may be responsible for regulating the mobilization of amino acids. Only the concentration of this amino acid was either lowered or uninfluenced during all four catabolic processes.

THE ANABOLIC EFFECTS OF CHORIONIC GONADOTROPIN IN NORMAL YOUNG MEN

It is now possible to ascribe an anabolic effect to the testicular secretion involving the deposition of protein and bone salts in somatic structures (1, 2). Such processes may be interpreted as contributing to the physiological spurts in height and weight during puberty and adolescence (1). As growth ceases and the youth moves toward the nitrogen equilibrium of maturity the influences of anabolic forces that operated clearly enough during active growth become uncertain. It may be presumed that the amounts of testicular secretion necessary to maintain the functions of the genitalia are no longer sufficient to exert progressive anabolic force elsewhere. Yet there is no indication that the capacity of somatic tissues to respond to androgens has reached its uttermost limit with the assumption of adult life. The anabolic effects of testosterone propionate may be well demonstrated to some degree and for a while in normal young men (3, 4) and even in advanced age (5). A multiplicity of subjects of all ages and with a variety of diseases have been found sensitive to testosterone propionate. Although the clinical circumstances have been too numerous and too complex for treatment here, ample evidence exists that serious resistance to the anabolic effects of the androgens must be rare indeed. The question now arises as to whether the secretory capacity of the mature testis is ever suf-

The anabolic influence of aminopyrine

Abstract Aminopyrine was anabolic when administered to 5 normal, young male subjects in usual therapeutic dosages, as indicated by diminished urinary nitrogen, creatine and inorganic phosphorus. The anabolic effect with the dosages of aminopyrine employed in this study was slightly less than but comparable in magnitude to that resulting from the intramuscular administration of 25 mg. daily of testosterone propionate. In 1 study the anticipated catabolic influence of intramuscular progesterone was partially offset by the simultaneous oral administration of aminopyrine. Although the effect of aminopyrine upon electrolyte metabolism was variable, a weak sodium retaining influence was suggested by the occurrence of sodium retention during treatment in 1 study and of moderate natriuresis in every instance after treatment was discontinued. Aminopyrine is a highly effective analgesic, antipyretic agent which has virtually been discarded from the therapeutic armamentarium because of the frequency of agranulocytosis associated with its administration. Renewed interest in aminopyrine or its congeners by clinical pharmacologists might be warranted on the basis of the anabolic property noted in this study.