Transthyretin is not essential for thyroxine to reach the brain and other tissues in transthyretin-null mice.
As part of a study on tissue uptake of thyroxine (T4) in a transthyretin (TTR)-null mouse strain, kinetic parameters of thyroxine metabolism in wild-type mice under normal physiological conditions are presented. Kinetic analysis of injected [(125)I]T4 showed that TTR-null mutants have markedly increased [(125)I]T4 transfer rate constants from plasma to the fast-exchange compartments of liver and kidney and from fast to slow kidney compartments. Transfer rates from plasma to brain, testes, and fat were little affected. The T4 tissue content in the mutants was greatly reduced in brain but relatively normal in liver and kidney. No major changes were observed in brain 3,3',5-triiodothyronine concentrations, suggesting that availability of this hormone is not markedly altered in the mutant mice. The low T4 brain content probably reflects the absence of T4-TTR complexes in the mutant choroid plexus and cerebrospinal fluid. This study indicates that TTR is not essential for T4 tissue uptake or for T4 to reach the brain across the choroid plexus-cerebrospinal fluid and/or blood-brain barriers.
Palha
J A
JA
Institute of Cancer Research, Columbia University, New York, New York 10032, USA.
Hays
M T
MT
Morreale de Escobar
G
G
Episkopou
V
V
Gottesman
M E
ME
Saraiva
M J
MJ
D000818:Animals; D001810:Blood Volume; D001921:Brain / Q000378:metabolism*; D008657:Metabolic Clearance Rate; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008954:Models, Biological; D011228:Prealbumin / Q000502:physiology*; D013974:Thyroxine / Q000378:metabolism*; D014018:Tissue Distribution; D014284:Triiodothyronine / Q000378:metabolism
D011228:Prealbumin; D014284:Triiodothyronine; D013974:Thyroxine