Serum rT3tracer kinetic studies were performed in 14 normal dogs and 9 normal human subjects. A number of models were used to evaluate the data. Relative rates of hormone degradation by rapidly equilibrating tissues such as liver and kidney and slowly equilibrating tissues such as muscle, skin, and brain could not be determined using serum data alone. Based on known physiology, all hormone losses were confined to rapidly equilibrating sites. Dogs had significantly higher mean serum total rT3(175% that in man), free fraction of rT3(437%), and free rT3levels (765%). Total rT3values were determined in different assays, due to species differences, which had similar anti-rT3antiserum characteristics and rT3standards. Fractional rates of rT3transfer from serum to both rapidly and slowly equilibrating pools in dogs were not significantly different from those in man, while the fractional transfer rate from the rapid pool to serum was increased (288%). This was associated with significantly smaller rapid and slow pool extravascular binding (rapid, 3.8%; slow, 2.8%), mass (29% and 21%, respectively), and volume (17% and 12%, respectively) in dogs compared to man. In dogs, 31% of the total 0.791 Mg rT3 was in serum, 29% was in the rapid pool, and 40% was in the slow pool compared to 16% of 2.677 μg in serum, 29% in the rapid pool, and 55% in the slow pool in man (P < 0.01). Further, 89% of the total unidirectional transfer from serum was to the rapid pool, and 11% to the slow pool in dogs compared to 82% and 18%, respectively, in man. Serum clearance (22%) and appearance rates (39%) as well as maximum total body production rates (34%) of rT3were lower in the dogs. Serum appearance and maximum production rates, and hormone masses in the rapid and slow pools were no longer significantly different between dogs and man when normalized for either body weight or body surface area. Serum volume was no longer significant when normalized for body surface area. Noncompart-mental analysis resulted in a significant underestimation of the mean total fraction rate of hormone exit from serum (by 20%), total volume of distribution (10%), extravascular binding (18%), and mean residence time (11%) in dogs and of extravascular binding (22%) in man. The serum appearance rate of rT3was 78% of the maximum total body production rate in dogs and 69% in man. These data indicate that compared to man the dog has lower binding of rT3to serum carrier proteins as well as to extravascular sites and relatively slower serum clearance rates and fractional rates of hormone transfer between serum and tissue sites. Only hormone production rates and masses appear to be related to differences in body size.
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