Abstract

Thyroid hormone control of tryptophan hydroxylase activity as well as of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid levels has been investigated in rat brain. Ontogenic studies demonstrated that at birth, whereas tryptophan hydroxylase activity was only 39%, the concentrations of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid were 30 and 66% of the adult values, respectively. Rapid increases in brain tryptophan hydroxylase, 5-hydroxytryptamine and 5-hydroxyindoleacetic acid were observed during the first 3 to 4 weeks of postnatal life. Neonatal thyroidectomy, produced by treatment of 1-day-old rats with ¹³⁵I, inhibited the developmental increases in brain tryptophan hydroxylase and 5-hydroxytryptamine. Whereas 50 µc of ¹³⁵I exerted no appreciable effect, 100 and 200 µc doses of the radioisotope led to a significant interference with the ontogenic increases in tryptophan hydroxylase activity and 5-hydroxytryptamine concentration. In contrast to the observed changes in tryptophan hydroxylase and 5-hydroxytryptamine, the levels of brain 5-hydroxyindoleacetic acid were increased in brains of hypothyroid rats. When administration of the radioisotope was delayed for 20 days after birth, no appreciable effect was seen on the developmental increases in brain tryptophan hydroxylase as well as 5-hydroxytryptamine or its metabolite, 5-hydroxyindoleacetic acid. Treatment of young cretinous rats with L-triiodothyronine restored the observed neurochemical changes in a dose- and time-dependent manner. However, when the initiation of L-triiodothyronine treatment was delayed until neonatally thyroidectomized rats had reached adulthood, this hormone failed to produce any significant change in the metabolism of brain 5-hydroxytryptamine. Our results indicate that thyroid hormone influences 5-hydroxytryptamine levels of developing brain and that a critical period exists in early postnatal life during which this hormone must be present in order to permit the normal ontogeny of the metabolism of this putative neurotransmitter.