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It has been confirmed that the oral administration of 17 α-methyltestosterone lowers the serum cholesterol concentrations of dogs fed a stock diet containing 3 Gm. of fat and 22 mg. of cholesterol per 100 Gm. The elevated serum cholesterol levels of cholesterol-fed euthyroid dogs, and of hypothyroid dogs fed a high fat diet, were significantly lowered by the oral administration of 17 α-methyltestosterone. The hypocholesteremic effect of 17 α-methyltestosterone was also observed in dogs maintained on a high fat-low cholesterol diet, but not on the same high fat diet supplemented with 1.5 per cent cholesterol. When 17 α-methyltestosterone was given by intramuscular injection in the same dosage as used for oral administration, the hypocholesteremic effect was more rapid and pronounced than that seen following oral administration; 17 α-methyltestosterone consistently lowered the cholesterol content of the α-lipoprotein fraction. Its effect on the β-fraction depended upon the composition of the diet.

17alpha-Methyltestosterone-4-(14)C was fed to two dogs in an experiment to determine tissue localization and metabolic disposition of this hypocholesterolemic steroid. No accumulation of the drug was found in any tissue, although a small amount of radioactivity was detected in the liver and the ileal mucosa of one animal. Most of the administered radio-activity was excreted in urine and feces. The urinary metabolites consisted largely of highly polar compounds which appeared resistant to glucuronidase treatment or solvolysis procedures. Analysis of the fecal metabolites showed the presence of unchanged methyltestosterone, of four isomeric methylandrostanediols, and of labeled unidentified polar compounds. Of the four identified methylandrostane-diols, the predominating fecal diols were 17alpha-methyl-5alpha-androstane-3beta,17beta-diol (45-62%) and 17alpha-methyl-5-androstane-3alpha,17-diol (12-28%); 17alpha-methyl-5alpha-androstane-3alpha,-17-diol and the 5beta:3beta isomer were found in very small amounts only.

In rats fed a stock diet, the oral administration of 17α-methyltestosterone (0.05% of the diet) produced a 46% average reduction of serum total cholesterol concentration. The ratio between the cholesterol content of the α- and β-lipoprotein fractions remained unchanged. In rats made mildly hypercholesterolemic by the addition of 1% cholesterol to the stock diet, the oral administration of 0.1% methyltestosterone prevented the rise in serum cholesterol concentration. This effect resulted primarily from a reduction of the cholesterol content of the α-lipoprotein fraction. The production of a more intense hypercholesterolemia by the administration of 1% cholesterol plus 0.5% cholic acid abolished the hypocholesterolemic action of 0.1% methyltestosterone. Analyses of the cholesterol content of the liver and intestinal wall indicated, in animals on both low and high cholesterol diets, that methyltestosterone did not exert its effect by producing a redistribution of the cholesterol between the serum and the tissues examined.

This report presents data on the rates of inactivation of 4 adipokinetic hypophysial peptides by adipose and extraadipose tissues of the rat and rabbit, and correlates these data with the in vitro and in vivo adipokinetic potencies of the peptides in these 2 species. The peptides under study (adrenocorticotropin, β-melanocyte-stimulating hormone, vasopressin and pituitary fraction H) were incubated for 1 hr with various tissue homogenates, and the adipokinetic activity remaining in the incubation mixture was then determined by introducing slices of rabbit, guinea pig, hamster or rat adipose tissue. The data showed: 1) Eight tissues of the rat (kidney, liver, adrenal, adipose tissue, lung, heart, testis and spleen) inactivate one or more of the peptides. 2) Ratios of the rates of inactivation of the 4 peptides vary markedly from one organ to another, and indicate the presence of at least 3 different inactivating enzymes in the rat. 3) While rat adipose tissue inactivates all 4 peptides under study, rabbit ...

T HE effects of drastic restriction of dietary fat intake and elimination of cholesterol intake upon serum lipid patterns in patients with hypertension have been presented previously as part of an investigation of the Kempner rice diet.’ This therapeutic diet, which contains no cholesterol, practically no fat and only minimal amounts of protein, is of particular interest in the study of lipid metabolism in man. The investigations previously reported gave rise to the following findings: (1) A moderate decline in the average serum cholesterol levels was seen in most patients on the rice diet; in no case did the levels decrease below the normal range. (2) A neutral fat lipemia, together with an increase in serum lipid phosphorus and a decreased percentage of esterified cholesterol, was observed in one-third of the patients. The decreased percentage of esterified cholesterol was associated with the development in some patients of marked sensitivity to dicumarol and of increased values for bromsulfthalein retention and thymol turbidity. This pointed to the possibility that the effects on the serum lipids were brought about through impairment of hepatic function. The present report extends the studies to a larger number of patients and in addition presents observations during lesser degrees of restriction of dietary fat and cholesterol. Data on serum lipoprotein concentrations, as determined with the ultracentrifuge, are presented. Several workers have correlated the serum cholesterol concentration in man with the dietary intake of cholesterol.2-6 Within a broad range of intake levels there was no correlation with the serum total cholesterol. However, the report by Starke of studies in Kempner’s clinic demonstrated that drastic restriction of both fat and cholesterol in the rice diet produced significant decreases in the free and esterified cholesterol of serum.6 Experimental studies in man by Keys,? by Hildreths and by Mayer9 and their co-workers indicated that the intake of fats, both animal and vegetable in origin, has a definite influence upon the serum cholestero1 level. On the other hand Kinsell and co-workers asserted that fats of vegetable origin do not tend to maintain high serum cholesterol levels and may even have a depressant effect. lo The weight reduction studies of Walker et al. showed that in the presence of low to moderate fat in the diet, the serum cholesterol and lipoproteins may vary in proportion to the total caloric intake.” Investigations of the effects of dietary variations upon the serum neutral fat or total lipids have not been reported, except in the previous communication from this laboratory. l Thus the lipemia observed in certain subjects during rice diet treatment has not received further elucidation.

Mephentermine, N-methyl-ω-phenyltertiary-butylamine, was compared with epinephrine, amphetamine, d-desoxyephedrine and Lephedrine. Although unique in lacking an asymmetric carbon atom and therefore not having a d- or l-form, its sympathomimetic properties are similar to those of the other β-phenylethylamines. It is less toxic to mice and causes less cerebral stimulation in chicks, cats, and dogs than amphetamine or d-desoxyephedrine. The pressor response and effect on heart rate in intact and vagotomized dogs are qualitatively and quantitatively similar to those of Gehedrine. Like l-ephedrine it constricts the small vessels of the nasal mucosa ant increases the air space of the nasal passage. Absorption following sinus instillation is minimal and is no greater than l-ephedrine. Unlike epinephrine it does not cause hyperglycemia in rabbits. It causes pupillary dilatation, is not anesthetic when applied topically to the cornea, is weakly spasmolytic for smooth muscle of intestine, and has no effect on tracheal cilia.