Studies of the Control of Thyroid Function in Rats: Effects of Salicylate and Related Drugs

Abstract

The mechanism by which salicylate depresses thyroid function has been investigated in normal rats. Bio-assay of TSH (thyroid stimulating hormone) in the plasma of rats was carried out using a modification of the McKenzie mouse procedure. It was demonstrated that the administration of salicylate, 2,4-dinitrophenol and [gamma] -resorcylate (2,6-dihydroxybenzoate) significantly depressed circulating TSH in association with a significant depression in plasma PBI (protein bound iodine). There was no effect of p-hydroxybenozate on plasma THS or plasma PBI. Previous suggestions that the hyper metabolism induced by salicylate and 2, 4-dinitrophenol was responsible for the depression in thyroid function may now be excluded, since [gamma] -resorcylate lacks this effect. Using the dialysis procedure of Chrlstensen for the determination of free thyroxine, it has been demonstrated that the in vitro addition of salicylate and [gamma] -resorcylate to rat serum increased the rate of dialysis of radlothyroxlne; p-hydroxy-benozate produced a smaller effect. Circulating free thyroxine was elevated after 52 hr. treatment with salicylate, 2,4-dinitrophenol and [image] -resorcylate, in spite of fall in plasma PBI, whereas there was no change following p-hydroxybenozate. Displacement of thyroxine from a fast-moving albumin fraction of rat serum proteins separated by starch gel electrophoresls was correlated with the increase in free thyroxine produced by the 3 drugs. The depression of TSH release induced by these drugs appears to be correlated with an increase in circulating free thyroxine. It is concluded that the level of circulating free thyroxine serves as the regulator of the negative feedback system controlling thyroid-pituitary interrelations.