This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by OTTEN, M. H. Articles by VISSER, T. J. Search for Related Content PubMed PubMed Citation Articles by OTTEN, M. H. Articles by VISSER, T. J.

Metabolism of 3,3'-Diiodothyronine in Rat Hepatocytes: Interaction of Sulfation with Deiodination^*

Department of Internal Medicine III and Clinical Endocrinology, Erasmus University Medical School Rotterdam, The Netherlands

Address requests for reprints to: Dr. T. J. Visser, Erasmus University Medical School, P.O. Box 1738,3000 DR Rotterdam, The Netherlands.

Abstract

Production of 3,3'-diiodothyronine (3,3'-T₂) is an important step in the peripheral metabolism of thyroid hormone in man. The rapid clearance of 3,3 '-T2 is accomplished to a large extent in the liver. We have studied in detail the mechanisms of this process using monolayers of freshly isolated rat hepatocytes. After incubation with 3,[3'-¹²⁵I]T₂, chromatographic analysis of the medium revealed two major metabolic routes: outer ring deiodination and sulfation. We recently demonstrated that sulfate conjugation precedes and in effect accelerates deiodination of 3,3'-T₂. In media containing different serum concentrations the cellular clearance rate was determined by the nonprotein-bound fraction of 3,3'-T₂. At substrate concentrations below 10^–8 M ¹²⁵I^– was the main product observed. At higher concentrations deiodination became saturated, and 3,3'-T₂ sulfate (T₂S) accumulated in the medium. Saturation of 3,3' -T₂ clearance was found to occur only at very high (>10^–6 M) substrate concentrations. The sulfating capacity of the cells exceeded that of deiodination by at least 20-fold. Deiodination was completely inhibited by 10^–4 M propylthiouracil or thiouracil, resulting in the accumulation of T₂S while clearance of 3,3'-T₂ was little affected. No effect was seen with methimazole. Hepatocytes from 72-h fasted rats showed a significant reduction of deiodination but unimpaired sulfation. Other iodothyronines interfered with 3,3'-T₂ metabolism. Deiodination was strongly inhibited by 2 µM T₄ and rT₃ (80%) but little by T₃ (15%), whereas the clearance of 3,3'-T2 was reduced by 27% (T₄ and rT₃) and 12% (T₃). It is concluded that the rapid hepatic clearance of 3,3'-T₂ is determined by the sulfate-transferring capacity of the liver cells. Subsequent outer ring deiodination of the intermediate T₂S is inhibited by propylthiouracil and by fasting, essentially without an effect on overall 3,3'-T₂ clearance. (Endocrinology 115: 887–894, 1984)

Footnotes

^* This work was supported in part by the Foundation for Medical Research FUNGO Grant 13-34-108 and by the Division for Health Research TNO Grant 13-34-110.

Received May 25, 1986.

This article has been cited by other articles:

				G. Pinna, O. Brodel, T. Visser, A. Jeitner, H. Grau, M. Eravci, H. Meinhold, and A. Baumgartner Concentrations of Seven Iodothyronine Metabolites in Brain Regions and the Liver of the Adult Rat Endocrinology, May 1, 2002; 143(5): 1789 - 1800. [Abstract] [Full Text] [PDF]

				J. Almeida Palha, R. Fernandes, G. Morreale de Escobar, V. Episkopou, M. Gottesman, and M. J. Saraiva Transthyretin Regulates Thyroid Hormone Levels in the Choroid Plexus, But Not in the Brain Parenchyma: Study in a Transthyretin-Null Mouse Model Endocrinology, September 1, 2000; 141(9): 3267 - 3272. [Abstract] [Full Text] [PDF]