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A B S T R A C T To study the metabolism of thyrotropinreleasing hormone (TRH) in vivo, 400 Ag TRH was administered intravenously to eight normal male subjects. Multiple plasma and urine samples were obtained before and after TRH administration. Serum TSH concentrations increased after TRH administration in all subjects. Plasma TRH levels, measured by radioimmunoassay, 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 metabolized and that a significant quantity of administered TRH is excreted in the urine. INTRODUCTIONThe administration of thyrotropin-releasing hormone (TRH)' to normal subjects is followed by a prompt increase in serum thyrotropin (TSH) concentrations.

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