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We administered 125Ithyroxine intravenously to adult male rats and measured uptake and subcellular distribution of the hormone and its metabolites in brain. Fractional brain uptake decreased after a large dose of iodothyronine, providing evidence for saturability of the uptake mechanism. Well-defined patterns of regional and subcellular labeling were noted within 1 h after 125Ithyroxine injection. Radioactivity in synaptosomes was always greater than in any other particle separated per gram of brain, increasing linearly relative to radioactivity in brain cytosol during the 1st h. Although 125Itriiodothyronine derived from 125Ithyroxine was not identified in serum at any time interval, it was measurable in synaptosomes within 20 min and in brain cytosol within 1 h after labeled hormone administration. Concentrations of the radioactive metabolite were twofold greater and ratios of 125Itriiodothyronine to 125Ithyroxine concentration were threefold greater in synaptosomes than in cytosol. Therefore, thyroxine may be converted to triiodothyronine within nerve terminals. Synaptosomal localization of iodothyronines and their metabolites may be relevant to the marked central and peripheral adrenergic nervous system effects of these aromatic amino acid hormones.
Dratman et al. (Fri,) studied this question.