Back to Search
Start Over
Tissue-Specific Alterations in Thyroid Hormone Homeostasis in Combined Mct10 and Mct8 Deficiency
- Source :
- Endocrinology, 155(1), 315-325. Endocrine Society, Endocrinology, 155(1), 315-325. The Endocrine Society
- Publication Year :
- 2014
- Publisher :
- Endocrine Society, 2014.
-
Abstract
- The monocarboxylate transporter Mct10 (Slc16a10; T-type amino acid transporter) facilitates the cellular transport of thyroid hormone (TH) and shows an overlapping expression with the well-established TH transporter Mct8. Because Mct8 deficiency is associated with distinct tissue-specific alterations in TH transport and metabolism, we speculated that Mct10 inactivation may compromise the tissue-specific TH homeostasis as well. However, analysis of Mct10 knockout (ko) mice revealed normal serum TH levels and tissue TH content in contrast to Mct8 ko mice that are characterized by high serum T3, low serum T4, decreased brain TH content, and increased tissue TH concentrations in the liver, kidneys, and thyroid gland. Surprisingly, mice deficient in both TH transporters (Mct10/Mct8 double knockout [dko] mice) showed normal serum T4 levels in the presence of elevated serum T3, indicating that the additional inactivation of Mct10 partially rescues the phenotype of Mct8 ko mice. As a consequence of the normal serum T4, brain T4 content and hypothalamic TRH expression were found to be normalized in the Mct10/Mct8 dko mice. In contrast, the hyperthyroid situation in liver, kidneys, and thyroid gland of Mct8 ko mice was even more severe in Mct10/Mct8 dko animals, suggesting that in these organs, both transporters contribute to the TH efflux. In summary, our data indicate that Mct10 indeed participates in tissue-specific TH transport and also contributes to the generation of the unusual serum TH profile characteristic for Mct8 deficiency.
- Subjects :
- Monocarboxylic Acid Transporters
Hypothalamo-Hypophyseal System
Thyroid Hormones
medicine.medical_specialty
Genotype
Thyroid Gland
610 Medicine & health
In situ hybridization
10052 Institute of Physiology
Mice
Endocrinology
Internal medicine
medicine
Animals
Homeostasis
Amino acid transporter
In Situ Hybridization
Mice, Knockout
Monocarboxylate transporter
Symporters
biology
Thyroid
Membrane Transport Proteins
Biological Transport
1310 Endocrinology
Mice, Inbred C57BL
Amino Acid Transport Systems, Neutral
medicine.anatomical_structure
Organ Specificity
Hypothalamus
10076 Center for Integrative Human Physiology
Mutation
Symporter
biology.protein
570 Life sciences
Female
Hormone
Subjects
Details
- ISSN :
- 19457170 and 00137227
- Volume :
- 155
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Endocrinology
- Accession number :
- edsair.doi.dedup.....a3145a7265ccad08108bb3d52fa42aff