Oral Presentation The International Congress of Neuroendocrinology 2014

Role of thyroid hormone transporters under physiological and pathological conditions (#93)

Heike Heuer

Thyroid hormone (TH) actions and metabolism are intracellular events that require the transport of TH across the plasma membrane. This process is facilitated by TH transporters of which the monocarboxylate transporter 8 (MCT8) has been most intensively analyzed. In humans, inactivating mutations in the X-linked MCT8 gene are associated with a severe form of psychomotor retardation in combination with abnormal serum TH parameters. The clinical picture (also known as Allan-Herndon-Dudley syndrome) clearly underscores the significance of MCT8 for proper brain development as well as TH metabolism and function. In mice, however, Mct8 deficiency does not grossly affect brain development whereas the endocrine abnormalities of the patients are fully replicated. Moreover, patients as well as MCT8 deficient mice exhibit a central resistance to thyroid hormone indicating that the hypothalamic as well as the pituitary sensing of TH is compromised. The exact function of MCT8 within the hypothalamus- pituitary system, however, needs still to be defined.

The aim of my presentation is to summarize the most recent findings concerning the physiological role of MCT8 as well as other TH transporters in the mouse brain. In particular, I will present an update on our studies of MCT8/OATP1C1 deficient mice that exhibit pronounced TH deprivation in the CNS.