Triiodothyronine treatment attenuates the induction of hepatic glycine N-methyltransferase by retinoic acid and elevates plasma homocysteine concentrations in rats

Kelly A. Tanghe, Tim A. Garrow, Kevin L. Schalinske

Research output: Contribution to journalArticle

Abstract

Recent studies indicated that hormonal imbalances have a role in modulating the metabolism of methyl groups and homocysteine, interrelated pathways that when disrupted, are associated with a number of pathologies. Retinoic acid (RA) was shown to induce hepatic glycine N-methyltransferase (GNMT), a key regulatory protein in methyl group metabolism, and to reduce circulating homocysteine levels. Because thyroid status influences the hepatic folate-dependent one-carbon pool and retinoids can alter thyroid hormone levels, the aim of this study was to examine the interaction between retinoids and thyroid function. For hypothyroid studies, rats were administered 0.5 g/L propylthiouracil in the drinking water for 15 d, and RA [30 μmol/(kg·d)] for the final 5 d. For hyperthyroid studies, rats were treated with RA [30 μmol/(kg·d)] for 8 d and triiodothyronine [T3; 50 μg/(100 g·d)] the last 4 d. T3 treatment prevented the RA-mediated increase in GNMT activity. However, GNMT abundance remained elevated, indicating that GNMT regulation by T3 in RA-treated rats may be, at least in part, at the post-translational level. In addition, T3 treatment elevated plasma levels of homocysteine 177%, an elevation that was prevented by RA. T 3-mediated hyperhomocysteinemia may be due to a 70% decrease in hepatic betaine-homocysteine S-methyltransferase, the enzyme that catalyzes folate-independent remethylation of homocysteine, whereas the RA-mediated stimulation of hepatic homocysteine remethylation by folate-dependent methionine synthase may contribute to lowering plasma homocysteine levels. These findings indicate that thyroid hormones, alone and in conjunction with RA, play an important role in the regulation of methyl group and homocysteine metabolism.

Original languageEnglish (US)
Pages (from-to)2913-2918
Number of pages6
JournalJournal of Nutrition
Volume134
Issue number11
DOIs
StatePublished - Nov 2004

Keywords

  • Glycine N-methyltransferase
  • Homocysteine
  • Rats
  • Retinoic acid
  • Thyroid

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

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