Richard L. Landau

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.

Care of patients.

Excerpt To the editor: The American medical profession is being criticized more vigorously than at any time in the past. Some of us have wondered why. Certainly the widespread attitude of disaffect...

The Metabolic Influence of Progestins

Information concerning the general metabolic, or what might be termed the systemic, effects of progesterone and synthetic progestins is reviewed. Included in the review, are sections on: 1) electrolyte metabolism, 2) protein metabolism, 3) growth hormone secretion, 4) carbohydrate metabolism, 5) fat metabolism, 6) respiratory effects, 7) the influence of synthetic progestins on electrolyte metabolism, and 8) the effect of synthetic progestins on electrolyte metabolism, and 8) the effect of synthetic progestins on protein metabolism. It appears that aldosterone and progesterone are the dominate endocrine factors regulating salt excretion during pregnancy. As 1 of the sex hormones, progesterone has a distinct growth-promoting influence on selected tissues of the accessory sex apparatus. Progesterone induces protein wasting which can be compensated for by the comsumption of added calories. It appears that progesterone is partially responsible for maintaining the positive energy balance in pregnant women, the appetite stimulus arising from the catabolic process which it initiates. Recent interest in the influence of progesterone and synthetic progestins on pituitary growth hormone secretion has come about both as a by-product of studies done on the effects of progestins on protein and carbohydrate metabolism and because of the known effects of other sex steroids on the output of this hormone. Progestins whether derived from testosterone or 17-alpha-hydroxyprogesterone when employed in the usual antiovulatory doses, and progesterone in amounts comparable to the levels achieved in the first half of pregnancy have no adverse effect on carbohydrate metabolism in normal men or women. However, in diabetics and perhaps in potential or prediabetics, 17-alpha-hydroxyprogesterone derivatives may cause slight deterioration in glucose tolerance. Circumstantial evidence has provided much support for the idea that some relationship exists between sex hormones and serum lipid content. A great number of synthetic and few natural derivatives of testosterone have ben evaluated with the purpose of developing a pharmacologically effective steroid with the full general protein anabolic activity of the male hormone but with minimal androgenic or virilizing potential.

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-

Metastatic pituitary carcinoma in a patient with acromegaly: a case report

IntroductionAsymptomatic pituitary abnormalities occur in about 10% of cranial magnetic resonance imaging scans, but metastatic carcinoma of the pituitary gland is rare: 133 cases have been reported. Two thirds secreted either prolactin or adrenocorticotropic hormone, and another 24% were non-secreting.Case presentationA 42-year-old Caucasian man lived for 30 years after the diagnosis of a pituitary tumor whose clinical and biochemical features were those of acromegaly and hypogonadism. Radiotherapy, totaling 7300 rad, was administered to the sella over two courses. Growth hormone levels normalized, but he developed both thyroid and adrenal insufficiency, and replacement therapy was commenced. Fourteen years later, growth hormone levels again became elevated, and bromocriptine was commenced but led to side effects that could not be tolerated. An attempted surgical intervention failed, and octreotide and pergolide were used in succession. Twenty-seven years after the diagnosis, a mass from an excisional biopsy of below the angle of the mandible proved to be metastatic pituitary carcinoma. Immunohistochemical staining was positive for synaptophysin, growth hormone, and prolactin. One year later, an octreotide scan showed uptake at the sella, neck, and spleen. Our patient declined further active oncology treatment.ConclusionsMetastatic pituitary carcinoma associated with acromegaly is particularly rare. To the best of our knowledge, this is the eighth such case and is the first report of growth hormone and prolactin present in the metastatic mass.

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.

Sociobiology: The New Synthesis by Edward O. Wilson (review)

This is a beautiful book with an immodest title and a grandiose mission. Most writers would stumble over this self-imposed environmental load, but Professor Wilson carries it off magnificently. It could well become the most influential book written for biological scientists in this decade. Its potential importance may be likened to that achieved by John Peters and Donald Van Sykes Quantitative Clinical Chemistry, which established a beachhead, set a style, and served as an articulate authoritative reference over a quarter of a century ago. For biologists or physicians, Sociobiology is a book which ought to be easily available to read or reread a chapter here or there as the spirit moves or when the mind needs refreshing. For specialists within the field of sociobiology, this must be the book