Concentrations of seven iodothyronine metabolites in brain regions and the liver of the adult rat

The concentrations of the iodothyronine metabolites T-4, T., 3,5-dilodothyronine (3,5-T-2), 3,3'-diiodothyronine (3,3'-T-2), reverse T-3 (rT(3)), 3,3'-T-2 sulfate (3,3T(2)S), and T-3 sulfate (T3S) were measured in 12 regions of the brain, the pituitary gland, and liver in adult male rats. Quantification of iodothyronine was performed by RLk following a newly developed method of purification and separation by HPLC. 3,5-T-2, 3,3'-T-2, rT(3) and T2S were detectable in the low femtomolar range (20-200 fmol/g) in most areas of the rat brain. T3S was detectable only in the hypothalamus. The concentrations of T-3 and T-4 were approximately 20- to 60-fold higher, ranging between 1 and 6 pmol/g. There was a significant negative correlation between the activities of inner-ring deiodinase and T-3 concentrations across brain areas. In the liver, 3,5-T-2, rT(3), and T3S were measurable in the low femtomolar range, whereas 3,3'-T-2 and 3,3T(2)S were not detectable. 3,5-T-2 and 3,3'-T-2 were not detectable in mitochondrial fractions of the brain regions. Tissue concentrations of 3,5-T-2 exhibited a circadian variation closely parallel to those of T-3 in the brain regions and liver. T-3 was not a substrate for outer-ring deiodination under different experimental conditions; thus, it remains unclear which substrate(s) and enzyme(s) are involved in the production of 3,5-T-2.. These results indicate that five iodothyronine metabolites other than T-3 and T-4 are detectable in the low femtomolar range in the rat brain and/or liver. The physiological implications of this finding are discussed.