PhD

thesisThe fate of testosterone administered intravenously in experimental animals has been investigated. The injected testosterone diffused rapidly from the circulation into various tissues of the body, the highest concentrations being found in fat. The testosterone was apparently not metabolized in the fatty tissues but was reabsorbed back into the circulation as it was removed by other structures. Evidence in presented to indicate that the liver and kidney is probable site of such metabolism. That other sites than liver and kidney might be involved in the metabolism of testosterone was indicated by studies in hepatectomized, nephrectomized animals in which less than 50% of the testosterone injected could be accounted for in a major proportion of the tissues. The metabolism of testosterone in human serum albumin given intravenously to human subjects was studied. In normal subjects an average of 74% of the injected testosterone was accounted for by an increased in urinary conjugated 17-ketosteroids during the post-injection period. An average of 63% was excreted during the first 24 hours with the major part of this excretion occurring during the first two hours. Following intravenous testosterone conjugated 17-ketosteroids were demonstrable in the plasmas. Maximum plasma level was found at 20 minutes after administration. The importance of the liver in the metabolism of testosterone was demonstrated by the lower concentrations of 17-ketosteroids in both the urine and plasma following administration of testosterone intravenously in a series of patients with liver disease. More than on pathway of testosterone metabolism was indicated by the much lower proportion of the injected hormone which was recovered as excess 17-ketosteroids in the cirrhotic patients in spite of the rapid disappearance and minimal excretion of the original steroid. After intravenous administration of testosterone to normal males the following steroids were isolated from the urine and identified: etiocholanol-3alpha-one-17, androsterone, etiocholanediol 3alpha, 17alpha and 3delta,5-androstadienone-17. It was further demonstrated that the androsterone and eitocholanolone which made up the greater part of the 17-ketosteroids in the urine were conjugated with glucuronic acid. No significant amounts of 3beta-hydroxysteroids were found in the ketonic fraction