THE EFFECTS OF PROPYLTHIOURACIL AND PERCHLORATE ON THE BIOGENESIS OF THYROID HORMONE1

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Abstract
Graded doses of propylthiouracil (PTU), administered to rats 30 minutes prior to tracer doses of I131 and 270 minutes prior to sacrifice, resulted in progressive reductions in total I131 uptake, I131 organic-uptake, and alterations in the relative proportions of the radioiodinated amino acids. Progressive blockade was associated with an increasing proportion of MIT, and a decreasing proportion of DIT and total thyro-nines. Comparable reductions in thyroidal I131 organic-uptake induced by perchlorate were not attended by alterations in relative composition of the radioiodinated amino acids. Administration of PTU to rats previously treated with TSH resulted in alterations in radioiodinated amino acid composition similar to those observed with PTU alone, despite a normal I131 organic-uptake. The effects of PTU cannot therefore be ascribed to the reduction in the flux of iodine into organic moieties. Triiodothyronine was detected in less than half of the glands from treatment-free controls and in none of the glands from PTU-treated rats in which a reduction in thyroxine formation occurred. These results indicate that PTU affects not only the initial oxidation of iodine and the resulting monoiodination of tyrosine, but also inhibits both the diiodination of tyrosyl residues and their coupling to form the hor-monally active iodothyronines. The findings provide a possible explanation for the restoration of a eumetabolic state in patients with Graves'' disease receiving PTU, whose I131 uptakes remain abnormally high.