In the male fish, transcriptions of corticotropin-releasing hormone (crh) and thyroid-stimulating hormone (tsh) in the brain were significantly up-regulated, probably as a compensation for hypothyroidism, but thyroglobulin (tg) and deiodinase 2 (dio2) were down-regulated in thyroid or liver.
These results indicate that D2 loss leads to significant changes in soleus contractile function and fiber type composition that are inconsistent with local hypothyroidism and suggest that reduced levels of PCG-1α may contribute to the observed phenotypical changes.
Furthermore, it was observed that the pituitary content of Dio2 mRNA was unaltered in hyperthyroidism but substantially elevated in hypothyroidism during the light phase.
Homozygous Dio2-deficient zebrafish were hypothyroid, displayed a delay in sexual maturity, and the duration of their reproductive period was substantially shortened.
One hypothesis is that a SNP (Thr92Ala) in DIO2 (required for local production of T3 out of T4) interferes with its kinetics and/or action, resulting in a local hypothyroid state in the brain.
In addition, residual symptoms of hypothyroidism have been linked to a prevalent polymorphism in the DIO2 gene that might be a risk factor for neurodegenerative disease.
This study investigates the clinical and biochemical response to L-T4 replacement therapy in hypothyroid patients in correlation with genetic variation in Deiodinase type ;; (DIO2) gene.
A polymorphism (Thr92Ala) in the gene encoding the deiodinase 2 (D2) enzyme that converts thyroxine to triiodothyronine in the brain was later identified in about 16% of hypothyroid persons.
Common variation in the DIO2 gene predicts baseline psychological well-being and response to combination thyroxine plus triiodothyronine therapy in hypothyroid patients.