Effect of testosterone and methy-testosterone on the creatine, creatinine and guanidoacetic acid levels of plasms and urine

As a direct result of this study the proposed role of methyl transferring agent for methyl-testosterone in creatine metabolism is no longer tenable. The level of guanidoacetic acid which is a precursor of the creatline increases as well as the creatine level following the administration of methyl-testosterone. While there has been no effort to show that the increase in creatine levels is the direct result of the increased formation of the guanidoacetic acid, it is at least indicated that the methyl-testosterone must act primarily at some stage prior to the guanidoacetic acid methylation. This observation is in agreement with the work of Samuels, Sellere and McCauley in which patients with severe hepatic disease still responded normally to methyl-testosterone administration. If the "methyl transfer" role of guanidoacetic acid were valid for the androgen, inter-ference with liver function should reflect in the methylation of guanidoacetic acid by the liver. In patients with severe nephritis the effect of methyl-testosterone was abolished. This too is in accord with the observations of the present work in that the androgen probably affects some process in the production of guanidoacetic acid. This production occurs in the kidney and consequently severe interference with kidney function should show abolition of the normally observed action of methyl-testosterone. The steroid nucleus as such was obviously not involved in the process of increased formation of guanidoacetic acid, since testosterone proprionate was ineffective. There is no evidence available at this time that would justify speculation as to the probable site of action of methyl-testosterone in the formation of creatine. The observed difference in the delay period preceding the elevation of plasma and urine levels of creatine is in agreement with previous observations. The probable explanation lies in the fact that the normal levels of the female are closer to the threshold values than are the normal male levels. Because of this the observed delay period in the females would reasonably be expected to be shorter. The relation of the thyroid to the existence of creatinuria should also be considered in reference to the difference in the delay periods noted with male and female subjects. Shelton and Tager studied the excretion of creatiine in a group of hypothyroid children and compared such excretion with that of a group of normal children. These workers showed that the excretion of creatine id definitely dimished in the hypothyroid cases. Thorn found that thyroid administration led to a creatinuria which often preceded the rise in basal metabolism. From these observations it is obviously necessary to evaluate the physical state of the subject in interpreting the elevations of the plasma and urine creatine levels. It is believed, however, that the difference between male and female subjects in the time of creatinuria appearance in response to methyl-testosterone administration may be influenced by thyroid activity, but certainly cannot be explained on this basis. The observed uniformity of response of the males in the long delay period and the females in the short delay period probably requires an explanation more complex than simple difference of thyroid activity.