Metabolism and Excretion of Exogenous Thyrotropin-Releasing Hormone in Humans

administered intravenously to eight normal male sub-jects. Multiple plasma and urine samples were obtained before and after TRH administration. Serum TSH con-centrations increased after TRH administration in all subjects. Plasma TRH levels, measured by radioimmuno-assay, were undetectable (< 0.4 ng/ml) before TRH administration. Plasma TRH concentrations averaged 33±7 ng/ml (mean +SEM) 2 min after TRH injection. Thereafter, they decreased rapidly so that the mean plasma TRH level was 2.9 ng/ml 20 min after TRH administration. The fall in plasma TRH levels was linear during this interval. Thereafter TRH levels declined more slowly. The mean half-life (ti) of TRH was 5.3±0.5 min. The mean distribution volume was 15.7 ±3.8 liters, an average of 16.5 % of body weight in these subjects. In the urine, 5.5±0.9 % of the administered TRH was recovered in the 3 h after TRH administration. Of the total urinary TRH recovered, 84.9 % was excreted in the first 30 min. These results indicate that TRH is distributed in a large volume, that it is rapidly metabo-lized and that a significant quantity of administered TRH is excreted in the urine