Tissue-Specific Thyroid Hormone Deprivation and Excess in Monocarboxylate Transporter (Mct) 8-Deficient Mice

• DOI: 10.1210/en.2006-0390
• Publication Date: 2006-05-19T00:35:00Z
• Authors: Alexandra M. Dumi...; Xiao-Hui Liao; Roy E. Weiss; Kathleen Millen; Samuel Refetoff
• Keywords: Monocarboxylate transporter

Mutations of the X-linked thyroid hormone (TH) transporter (monocarboxylate transporter, MCT8) produce in humans unusual abnormalities function characterized by high serum T3 and low T4 rT3. The mechanism these changes remains obscure raises questions regarding regulation intracellular availability metabolism TH. To study pathophysiology MCT8 deficiency, we generated Mct8 knockout mice. Male mice deficient (Mct8(-/y)) replicate observed affected men. TH deprivation replacement with L-T3 showed that suppression TSH required higher levels Mct8(-/y) than wild-type (WT) littermates, indicating hypothalamus and/or thyrotroph resistance to T3. Furthermore, is maintain level because latter was not different between two genotypes during administration have 2.3-fold content liver associated 6.1- 3.1-fold increase deiodinase 1 mRNA enzymatic activity, respectively. relative excess produced a decrease cholesterol (79 +/- 18 vs. 137 38 mg/dl WT) an alkaline phosphatase (107 23 58 3 U/liter levels. In contrast, cerebrum 1.8-fold lower mice, 1.6- 10.6-fold D2 respectively, as previously TH-deprived WT We conclude cell-specific differences due contribution various transporters are responsible for clinical presentation this defect, contrast deficiency.