To determine whether ethanol per se affects testosterone metabolism, alcohol was administered to normal male volunteers for periods up to four weeks, resulting in an initial dampening of the episodic bursts of testosterone secretion followed by decreases in both the mean plasma concentration and the production rate of testosterone. The volunteers received adequate nutrition and none lost weight during the study, which tended to exclude a nutritional disturbance as the cause of the decreased testosterone levels. The changes in plasma luteinizing hormone suggested both a central (hypothalamus-pituitary) and gonadal effect of alcohol. In addition, alcohol consumption increased the metabolic clearance rate of testosterone in most subjects studied, probably owing to the combined effects of a decreased plasma binding capacity for the androgen and increased hepatic testosterone A-ring reductase activity. These results indicate that alcohol markedly affects testosterone metabolism independently of cirrhosis or nutritional factors.

In a large variety of apparently unrelated diseases, the major pathway of tryptophan metabolism, that which proceeds through kynurenine, has been observed to be abnormal. The deviation is a quantitative one: the urinary excretion of one or more normal metabolites is high. Attempts to explain this phenomenon have largely been restricted to hypotheses that assume a "metabolic block" in the catabolism of these metabolites, as exemplified by pyridoxine deficiency. However, it seems unlikely that the variety of conditions associated with the increased excretion of these tryptophan metabolites, e.g., Hodgkin's disease, rheumatoid arthritis, schizophrenia, porphyria, renal tuberculosis, and aplastic anemia, to mention only a few that are included in a recent review (1), would all be coupled specifically with pyridoxine deficiency. Being inducible by its specific substrate (6) and, through a different mechanism involving RNA synthesis (7), by glucocorticoids (8, 9), it has served as the model of mammalian adaptive enzymes and has drawn attention to the important physiological regulation of metabolism mediated by changes in the amounts of enzymes (10, 4). The quantitative study of tryptophan pyrrolase in human liver appeared to be necessary for approaching the causes that underlie the abnormal tryptophan metabolism in various diseases. MethodsThe hospitalized subjects with various diseases were all ambulatory and in no acute distress, with the indicated exception of those who were undergoing abdominal surgery. They were kept on a regular hospital diet and received no medications for at least 1 week before, and during, these studies. Unless otherwise indicated, no pa--tient was included who had been taking corticosteroids, sedatives, tranquilizers, or vitamin preparations for a prolonged period of time. The urinary excretion of kynurenine during the 24 hours after an oral dose of 2 g L-tryptophan was determined by the method of Tompsett (11).Specimens of human liver were obtained by Menghini needle biopsy by the standard percutaneous aspiration technique. When indicated, larger liver samples were obtained by excision from surgical patients during laparotomy. With these larger samples, a microassay suitable 1527

were made. All species of spermatozoa tested, including those highly sensitive-to an increase in osmotic pressure, were fully motile in 20M glycerol. It is most unlikely that cells impermeable to glycerol would retain motility in the presence of such an excessive external osmotic pressure, and the retention of motility in the presence of high concentrations of glycerol was taken as evidence that the cells were permeated by this solute. Other neutral solutes can to some extent protect spermatozoa against damage by freezing and thawing (Smith & Polge, 1950), but none is as effective as glycerol. SUMMARY 1. The spermatozoa of the rabbit, the bull, the fowl and the herring were subjected to freezing and thawing in media containing various concentrations of glycerol, and observations made of the resulting changes in motility of the spermatozoa. 2. These observations indicated that the damage suffered by the spermatozoa during freezing and thawing was caused-by their exposure to excessive concentrations of salt when water was removed as ice. 3. The concentration of electrolyte above which irreversible damage occurred was characteristic for the spermatozoa of each species tested. The protective action of glycerol was due to its ability to prevent the salt concentration rising above this level.

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