The monocarboxylate transporter 8 linked to human psychomotor retardation is highly expressed in thyroid hormone-sensitive neuron populations

Endocrinology. 2005 Apr;146(4):1701-6. doi: 10.1210/en.2004-1179. Epub 2005 Jan 20.

Abstract

Recent genetic analysis in several patients presenting a severe form of X-linked psychomotor retardation combined with abnormal thyroid hormone (TH) levels have revealed mutations or deletions in the gene of the monocarboxylate transporter 8 (MCT8). Because in vitro MCT8 functions as a TH transporter, the complex clinical picture of these patients indicated an important role for MCT8 in TH-dependent processes of brain development. To provide a clue to the cellular function of MCT8 in brain, we studied the expression of MCT8 mRNA in the murine central nervous system by in situ hybridization histochemistry. In addition to the choroid plexus structures, the highest transcript levels were found in neo- and allocortical regions (e.g. olfactory bulb, cerebral cortex, hippocampus, and amygdala), moderate signal intensities in striatum and cerebellum, and low levels in a few neuroendocrine nuclei. Colocalization studies revealed that MCT8 is predominantly expressed in neurons. Together with the spatiotemporal expression pattern of MCT8 during the perinatal period, these results strongly indicate that MCT8 plays an important role for proper central nervous system development by transporting TH into neurons as its main target cells.

MeSH terms

  • Animals
  • Brain / metabolism*
  • Carrier Proteins / genetics*
  • Female
  • Humans
  • Iodide Peroxidase / genetics
  • Iodothyronine Deiodinase Type II
  • Male
  • Mice
  • Monocarboxylic Acid Transporters / genetics*
  • Monocarboxylic Acid Transporters / physiology*
  • Neurons / metabolism*
  • Organic Cation Transport Proteins / genetics
  • Psychomotor Disorders / genetics*
  • RNA, Messenger / analysis*
  • Symporters
  • Thyroid Hormones / metabolism*

Substances

  • Carrier Proteins
  • Monocarboxylic Acid Transporters
  • Oatp2 protein, mouse
  • Organic Cation Transport Proteins
  • RNA, Messenger
  • SLC16A2 protein, human
  • Symporters
  • Thyroid Hormones
  • Iodide Peroxidase