Editing Iodothyronine deiodinase (section)

== Function ==

Deiodinase 1 both activates T<sub>4</sub> to produce T<sub>3</sub> and inactivates T<sub>4</sub>.  Besides its increased function in producing extrathyroid T<sub>3</sub> in patients with [[hyperthyroidism]], its function is less well understood than D2 or D3 <ref name="pmid17016550" /><ref name="pmid18815314"/>  Deiodinase 2, located in the ER membrane, converts T<sub>4</sub> into T<sub>3</sub> and is a major source of the cytoplasmic T<sub>3</sub> pool.<ref name="pmid17016550" />  Deiodinase 3 prevents T<sub>4</sub> activation and inactivates T<sub>3</sub>.<ref name="url_Bianco_Lab"/>  D2 and D3 are important in homeostatic regulation in maintaining T<sub>3</sub> levels at the plasma and cellular levels.  In hyperthyroidism D2 is down regulated and D3 is upregulated to clear extra T<sub>3</sub>, while in [[hypothyroidism]] D2 is upregulated and D3 is downregulated to increase cytoplasmic T<sub>3</sub> levels.<ref name="pmid17016550" /><ref name="pmid18815314"/>

Serum T<sub>3</sub> levels remain fairly constant in healthy individuals, but D2 and D3 can regulate tissue specific intracellular levels of T<sub>3</sub> to maintain [[homeostasis]] since T<sub>3</sub> and T<sub>4</sub> levels may vary by organ.  Deiodinases also provide spatial and temporal developmental control of thyroid hormone levels.  D3 levels are highest early in development and decrease over time, while D2 levels are high at moments of significant metamorphic change in tissues.  Thus D2 enables production of sufficient T<sub>3</sub> at necessary time points while D3 may shield tissue from overexposure to T<sub>3</sub>.<ref name="pmid9292958"/>

Also, iodothyronine deiodinases (type 2 y 3; DIO2 and DIO3, respectively) respond to seasonal changes in [[Photoperiodism|photoperiod]]-driven [[melatonin]] secretion and govern peri-hypothalamic catabolism of the prohormone thyroxine (T4). In long summer days, the production of hypothalamic T3 increase due to DIO-2-mediated conversion of T4 to the biologically active hormone. This process allows to active  anabolic neuroendocrine pathways that maintain reproductive competence and increase body weight. However, during the adaptation to reproductively inhibitory photoperiods, the levels of T3 decrease due to peri-hypothalamic DIO3 expression that catabolizes T4 and T3 into receptor inactive amines.<ref>{{cite journal | vauthors = Bao R, Onishi KG, Tolla E, Ebling FJ, Lewis JE, Anderson RL, Barrett P, Prendergast BJ, Stevenson TJ | display-authors = 6 | title = Genome sequencing and transcriptome analyses of the Siberian hamster hypothalamus identify mechanisms for seasonal energy balance | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 116 | issue = 26 | pages = 13116–13121 | date = June 2019 | pmid = 31189592 | pmc = 6600942 | doi = 10.1073/pnas.1902896116 | bibcode = 2019PNAS..11613116B | doi-access = free }}</ref><ref>{{cite journal | vauthors = Barrett P, Ebling FJ, Schuhler S, Wilson D, Ross AW, Warner A, Jethwa P, Boelen A, Visser TJ, Ozanne DM, Archer ZA, Mercer JG, Morgan PJ | display-authors = 6 | title = Hypothalamic thyroid hormone catabolism acts as a gatekeeper for the seasonal control of body weight and reproduction | journal = Endocrinology | volume = 148 | issue = 8 | pages = 3608–17 | date = August 2007 | pmid = 17478556 | doi = 10.1210/en.2007-0316 | doi-access = free }}</ref>

Deiodinase 2 also plays a significant role in [[thermogenesis]] in [[brown adipose tissue]] (BAT).  In response to sympathetic stimulation, dropping temperature, or overfeeding BAT, D2 increases oxidation of fatty acids and uncouples oxidative phosphorylation via uncoupling protein, causing mitochondrial heat production.  D2 increases during cold stress in BAT and increases intracellular T<sub>3</sub> levels.  In D2 deficient models, shivering is a behavioral adaptation to the cold.  However, heat production is much less efficient than uncoupling lipid oxidation.<ref name="pmid3793928">{{cite journal | vauthors = Bianco AC, Silva JE | title = Intracellular conversion of thyroxine to triiodothyronine is required for the optimal thermogenic function of brown adipose tissue | journal = The Journal of Clinical Investigation | volume = 79 | issue = 1 | pages = 295–300 | date = January 1987 | pmid = 3793928 | pmc = 424048 | doi = 10.1172/JCI112798 }}</ref><ref name="pmid11696583">{{cite journal | vauthors = de Jesus LA, Carvalho SD, Ribeiro MO, Schneider M, Kim SW, Harney JW, Larsen PR, Bianco AC | display-authors = 6 | title = The type 2 iodothyronine deiodinase is essential for adaptive thermogenesis in brown adipose tissue | journal = The Journal of Clinical Investigation | volume = 108 | issue = 9 | pages = 1379–85 | date = November 2001 | pmid = 11696583 | pmc = 209445 | doi = 10.1172/JCI13803 }}</ref>