Increased thyroxine secretion following administration of dinitrophenol to rats

1. Feeding male rats 0.2% dinitrophenol (DNP) in the diet caused weight loss, a significant fall in the plasma protein bound iodine concentration, and a rise in the thyroxine secretion rate. Thyroxine concentration was raised in the liver and intestinal tract with contents, reduced in the carcass, and unchanged in the pelt.2. Radio-iodine uptake by the thyroid gland was unchanged but there was a significant fall in the thyroid/serum activity ratio.3. Five hours after tracer radiothyroxine, DNP treated rats had a reduced fraction of dose in the plasma, with raised concentrations in the liver and intestines.4. Fractional turnover rates of radiothyroxine in plasma, liver and carcass were raised in DNP treated animals.5. DNP caused a significant increase in the biliary clearance of radiothyroxine, when measured immediately after administration of tracer and 4 hr later.6. It is postulated that DNP displaces thyroxine from its plasma binding proteins and that the displaced hormone is excreted in the bile. This wastage together with increased demand resulting from DNP induced hypermetabolism results in increased output of thyroxine by the thyroid gland.