Deiodinases are well known to thyroid aficionados as enzymes that can activate product of the thyroid gland, by converting it to 3,5,30- triiodothyironine (T3), the molecule ultimately responsible for thyroid hormone–regulated gene transcription. For about 40 years now, it has been well documented that most circulating T3 (>80% in humans) originates from outside of the thyroid parenchyma, via the actions of the types 1 and 2 iodothyr- onine deiodinases (D1 and D2, respectively) (1). Although D1 has low affinity for T4 when compared to D2, it still plays a role in T3 production because it is expressed at very high levels in some tissues (2). Clinically, two single nucleotide polymorphisms in the 30 untranslated region of the human D1 mRNA (D1a-C=T at position 785 and D1b-A=G at position 1814) were shown to be associated with the ratios of serum thyroid hormone levels (3), while the D1a (785-T) was asso- ciated with enhanced potentiation of the antidepressant effect of sertraline by T3 (4). At the same time, clues obtained from the D1 knockout mouse hint that D1 might also affect thyroid economy by playing a scavenger role (5). Conjugated iodo- thyronines have increased water solubility and are thus preferentially eliminated in the urine and bile. However, loss of iodine through these pathways is minimized because conjugated iodothyronines are excellent substrates for D1, which is highly expressed in liver and kidneys.
Covering the Base-Pairs in Iodothyronine Deiodinase-1 Biology: Holes Remain in the Lineup.
Bala ́zs Gereben, D.V.M., Ph.D., and Antonio C. Bianco, M.D., Ph.D.Thyroid, 2009; doi: 10.1089=thy.2009.1593