The effect of methyltestosterone on the rate of synthesis of creatine.

After the daily administration of methyltestosterone to normal human subjects for several weeks, creatine usually appears in the urine in gradually increasing amounts (1,2). Because the creatinuria so induced is associated with an increase in the concentration of serum creatine, and also because the amount of urinary creatinine increases, it has been generally assumed that the synthesis of creatine is accelerated by methyltestosterone. The effect of methyltestosterone on the metabolism of creatine can be more directly observed by measuring the rate of turnover of creatine by isotope methods. It has previously been shown that the rate of dilution of labeled body creatine, as reflected in the concentration of isotope in urinary creatinine, is a measure of the rate of replacement of depot creatine by endogenous creatine (3-5). By so tagging the body creatine of a normal male subject subsisting on a diet as free of creatine and creatinine as possible, the rate of synthesis of creatine before and during the administration of methyltestosterone has been measured. Evidence will be presented that methyltestosterone does increase the rate of synthesis of creatine. That this is specifically brought about by its effect on the reaction or reactions involved in the formation of guanidoacetic acid is indicated by other data.