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Int J Mol Sci. 2018 Jun 19;19(6). pii: E1804. doi: 10.3390/ijms19061804.

The Type 3 Deiodinase: Epigenetic Control of Brain Thyroid Hormone Action and Neurological Function.

Author information

1
Center for Molecular Medicine, Maine Medical Center Research Institute, Maine Medical Center, Scarborough, ME 04074, USA. hernaa@mmc.org.
2
Graduate School for Biomedical Science and Engineering, University of Maine, Orono, ME 04469, USA. hernaa@mmc.org.
3
Department of Medicine, Tufts University School of Medicine, Boston, MA 02111, USA. hernaa@mmc.org.
4
Center for Molecular Medicine, Maine Medical Center Research Institute, Maine Medical Center, Scarborough, ME 04074, USA. stohnp@mmc.org.

Abstract

Thyroid hormones (THs) influence multiple processes in the developing and adult central nervous system, and their local availability needs to be maintained at levels that are tailored to the requirements of their biological targets. The local complement of TH transporters, deiodinase enzymes, and receptors is critical to ensure specific levels of TH action in neural cells. The type 3 iodothyronine deiodinase (DIO3) inactivates THs and is highly present in the developing and adult brain, where it limits their availability and action. DIO3 deficiency in mice results in a host of neurodevelopmental and behavioral abnormalities, demonstrating the deleterious effects of TH excess, and revealing the critical role of DIO3 in the regulation of TH action in the brain. The fact the Dio3 is an imprinted gene and that its allelic expression pattern varies across brain regions and during development introduces an additional level of control to deliver specific levels of hormone action in the central nervous system (CNS). The sensitive epigenetic nature of the mechanisms controlling the genomic imprinting of Dio3 renders brain TH action particularly susceptible to disruption due to exogenous treatments and environmental exposures, with potential implications for the etiology of human neurodevelopmental disorders.

KEYWORDS:

Dio3; Dlk1-Dio3 genomic imprinting; behavior; brain development; brain morphology; environmental factors; neuroendocrine function; sensory function; thyroid hormone; type 3 deiodinase

PMID:
29921775
PMCID:
PMC6032375
DOI:
10.3390/ijms19061804
[Indexed for MEDLINE]
Free PMC Article

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