Abstract:
:Choroid plexus has the highest concentration of transthyretin (TTR) mRNA in the body, 4.4 microg TTR mRNA/g wet weight tissue, compared with 0.39 microg in the liver. The proportion of TTR to total protein synthesis in choroid plexus is 12%. All newly synthesized TTR is secreted towards the ventricles. Net transfer of T4 occurs only towards the ventricle and depends on ongoing protein synthesis. Thyroxine-binding globulin (TBG), TTR and albumin form a "buffering" system for plasma [T4] because of their overlapping affinities and on/off rates for L-thyroxine (T4)-binding. The individual components of this network determining T4 distribution are functionally highly redundant. Absence of TBG (humans), or TTR (mice), or albumin (humans, rats) is not associated with hypothyroidism. Natural selection is based on small, inheritable alterations improving function. The study of these alterations can identify function. TTR genes were cloned and sequenced for a large number of vertebrate species. Systematic, stepwise changes during evolution occurred only in the N-terminal region, which became shorter and more hydrophilic. Simultaneously, a change in function occurred: TTR affinities for T4 are higher in mammals than in reptiles and birds. L-triiodothyronine (T3) affinities show the opposite trend. This favors site-specific regulation of thyroid hormones by tissue-specific deiodinases in the brain.
journal_name
Clin Chem Lab Medjournal_title
Clinical chemistry and laboratory medicineauthors
Schreiber Gdoi
10.1515/CCLM.2002.210keywords:
subject
Has Abstractpub_date
2002-12-01 00:00:00pages
1200-10issue
12eissn
1434-6621issn
1437-4331journal_volume
40pub_type
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