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. 1982 Apr;69(4):799–808. doi: 10.1172/JCI110519

Effect of Alterations in Thyroid Status on the Metabolism of Thyroxine and Triiodothyronine by Rat Pituitary Gland In Vitro

Michiko Maeda 1,2,3,4, Sidney H Ingbar 1,2,3,4
PMCID: PMC370134  PMID: 7076849

Abstract

The metabolism of thyroxine (T4) was studied in slices of rat pituitary gland and liver from the same animal incubated in vitro with [125I]T4 and 10 mM dithiothreitol. In the pituitary gland, generation of 125I-labeled 3,5,3′-triiodothyronine (T3), as well as overall T4 degradation, increased significantly at 24 h after thyroidectomy and by 2 wk were approximately five times control values. Conversely, following a single injection of T3 (1.5 μg/100 g body wt), values for both functions were significantly decreased at 4 h, and reached a nadir of ∼20% of control values at 12 and 24 h. Net T3-neogenesis accounted for ∼70% of T4 degradation in control pituitaries from intact rats. This proportion was increased by thyroidectomy and decreased by T3 replacement. Indirect evidence indicated that thyroidectomy decreased, and T3 administration increased, non-T3 generating pathways of T4 metabolism, probably 5-monodeiodination leading to formation of 3,3′5′-triiodothyronine (rT3). As judged from studies by others, the prompt changes in T4 metabolism that followed thyroidectomy or T3 administration could not be explained by changes in pituitary cell type. Changes in T3-neogenesis in liver were the converse of those in pituitary, and were much slower to occur.

In the thyroidectomized rat, administration of cycloheximide resulted in an ∼60% inhibition of pituitary T3-neogenesis and T4-degradation at 4 h, a time-course of inhibition similar to that produced by T3. Unlike T3, cycloheximide did not alter the proportion of T4 degradation that could be accounted for by T3 neogenesis, and appeared, therefore, to inhibit both T3 generating and non-T3 generating pathways. The time-course of the inhibitory effect of cycloheximide on the incorporation of [3H]leucine into hemipituitaries in vitro was parallel to its effect on T3-neogenesis. The inhibition of T3-neogenesis that occurred when T3 and cycloheximide were given together did not exceed the effect of T3 alone, suggesting a common mechanism of action of the two agents.

From the foregoing information, the following tentative conclusions are drawn: (a) turnover of the 5′-monodeiodinase for T4 in rat pituitary is rapid, substantially more so than in liver; (b) thyroidectomy enhances, and T3 inhibits, the conversion of T4 to T3 in the pituitary; these manipulations have opposite effecs on the non-T3 generating pathways of T4 metabolism, probably the 5-monodeiodination of T4 that produces rT3; (c) these changes are probably the result of parallel effects on the synthesis of the corresponding enzymes; (d) the changes in T3-neogenesis described may permit an intrapituitary feedback mechanism that damps the changes in TSH secretion mediated by classical feedback regulatory control; (e) the effects of hypothyroidism and T3-replacement on T3-neogenesis and overall T4 degradation in liver were opposite to those produced in the pituitary. Hence, among differing tissues, the same stimuli may produce greatly different responses in pathways of peripheral T4 metabolism, thus making possible differing metabolic sequelae within each.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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