Transthyretin regulates thyroid hormone levels in the choroid plexus, but not in the brain parenchyma: Study in a transthyretin-null mouse model

Transthyretin (TTR) is the major T-4-binding protein in rodents. Using a TT R-null mouse model we asked the following questions. 1) Do other T-4 bindin g moieties replace TTR in the cerebrospinal fluid (CSF)? 2) Are the low who le brain total T-4 levels found in this mouse model associated with hypothy roidism, e.g. increased 5'-deiodinase type 2 (D2) activity and RC3-neurogra nin messenger RNA levels? 3) Which brain regions account for the decreased total whole brain T-4 levels? 4) Are there changes in T-3 levels in the bra in? Our results show the following. 1) No other T-4-binding protein replace s TTR in the CSF of the TTR-null mice. 2) D2 activity is normal in the cort ex, cerebellum, and hippocampus, and total brain RC3-neurogranin messenger RNA levels are not altered. 3) T-4 levels measured in the cortex, cerebellu m, and hippocampus are normal. However T-4 and T-3 levels in the choroid pl exus are only 14% and 48% of the normal values, respectively. 4) T-3 levels are normal in the brain parenchyma. The data presented here suggest that T TR influences thyroid hormone levels in the choroid plexus, but not in the brain. Interference with the blood-choroid-plexus-CSF-TTR-mediated route of T-4 entry into the brain caused by the absence of TTR does not produce mea surable features of hypothyroidism. It thus appears that TTR is not require d for T-4 entry or for maintenance of the euthyroid state in the mouse brai n.