The Evolution of Transthyretin Synthesis in the Choroid Plexus
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Gerhard Schreiber
Abstract
Choroid plexus has the highest concentration of transthyretin (TTR) mRNA in the body, 4.4 μg TTR mRNA/g wet weight tissue, compared with 0.39 μg 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.
Copyright © 2002 by Walter de Gruyter GmbH & Co. KG
Articles in the same Issue
- Author Index
- Subject Index
- Contents
- Historical Aspects and Perspectives in Transthyretin Research
- Transthyretin from Discovery to Now
- The Evolution of Transthyretin Synthesis in Vertebrate Liver, in Primitive Eukaryotes and in Bacteria
- The Evolution of Transthyretin Synthesis in the Choroid Plexus
- Hepatic Synthesis, Maturation and Complex Formation between Retinol-Binding Protein and Transthyretin
- Synthesis and Structural Analysis of the N-Terminal Domain of the Thyroid Hormone-Binding Protein Transthyretin
- Three-Dimensional Structure of the Transthyretin-Retinol-Binding Protein Complex
- Mechanisms of Molecular Recognition: Crystal Structure Analysis of Human and Rat Transthyretin Inhibitor Complexes
- Transthyretin in Fish: State of the Art
- The Effects of Endocrine-Disrupting Chemicals on Thyroid Hormone Binding to Xenopus laevis Transthyretin and Thyroid Hormone Receptor
- Clinical Picture and Outcome of Transthyretin-Related Familial Amyloid Polyneuropathy (FAP) in Japanese Patients
- Laboratory Assessment of Transthyretin Amyloidosis
- Amyloid: Morphology and Toxicity
- Historical Overview of Analytical Methods for the Measurement of Transthyretin
- Nutritional Regulation of Visceral Markers in Rat Liver and Cultured Hepatoma Cells
- Significance of Transthyretin in Protein Metabolism
- Transthyretin as a Thyroid Hormone Carrier: Function Revisited
- The Molar Ratio of Retinol-Binding Protein to Transthyretin in the Assessment of Vitamin A Status in Adults. Proposal of a Cut-off Point
- Observations with Regard to the National Kidney Foundation K/DOQI Clinical Practice Guidelines Concerning Serum Transthyretin in Chronic Renal Failure
- Metabolism and Clinical Interest of Serum Transthyretin (Prealbumin) in Dialysis Patients
- Protein Status in Pancreatitis – Transthyretin Is a Sensitive Biomarker of Malnutrition in Acute and Chronic Pancreatitis
- Assessment of Nutritional Status in Organ Transplant: Is Transthyretin a Reliable Indicator?
- Body Composition and Nutritional Parameters in HIV and AIDS Patients
- C-Reactive Protein to Transthyretin Ratio for the Early Diagnosis and Follow-up of Postoperative Infection
- The Prognostic Value of Nutritional and Inflammatory Indices in Critically Ill Patients with Acute Respiratory Failure
- Transthyretin: Its Response to Malnutrition and Stress Injury. Clinical Usefulness and Economic Implications
- Transthyretin Measurement as a Screening Tool for Protein Calorie Malnutrition in Emergency Hospital Admissions
- Outcomes of Continuous Process Improvement of a Nutritional Care Program Incorporating TTR Measurement
- The Role of Visceral Protein Markers in Protein Calorie Malnutrition
- Acknowledgement
- Meetings
Articles in the same Issue
- Author Index
- Subject Index
- Contents
- Historical Aspects and Perspectives in Transthyretin Research
- Transthyretin from Discovery to Now
- The Evolution of Transthyretin Synthesis in Vertebrate Liver, in Primitive Eukaryotes and in Bacteria
- The Evolution of Transthyretin Synthesis in the Choroid Plexus
- Hepatic Synthesis, Maturation and Complex Formation between Retinol-Binding Protein and Transthyretin
- Synthesis and Structural Analysis of the N-Terminal Domain of the Thyroid Hormone-Binding Protein Transthyretin
- Three-Dimensional Structure of the Transthyretin-Retinol-Binding Protein Complex
- Mechanisms of Molecular Recognition: Crystal Structure Analysis of Human and Rat Transthyretin Inhibitor Complexes
- Transthyretin in Fish: State of the Art
- The Effects of Endocrine-Disrupting Chemicals on Thyroid Hormone Binding to Xenopus laevis Transthyretin and Thyroid Hormone Receptor
- Clinical Picture and Outcome of Transthyretin-Related Familial Amyloid Polyneuropathy (FAP) in Japanese Patients
- Laboratory Assessment of Transthyretin Amyloidosis
- Amyloid: Morphology and Toxicity
- Historical Overview of Analytical Methods for the Measurement of Transthyretin
- Nutritional Regulation of Visceral Markers in Rat Liver and Cultured Hepatoma Cells
- Significance of Transthyretin in Protein Metabolism
- Transthyretin as a Thyroid Hormone Carrier: Function Revisited
- The Molar Ratio of Retinol-Binding Protein to Transthyretin in the Assessment of Vitamin A Status in Adults. Proposal of a Cut-off Point
- Observations with Regard to the National Kidney Foundation K/DOQI Clinical Practice Guidelines Concerning Serum Transthyretin in Chronic Renal Failure
- Metabolism and Clinical Interest of Serum Transthyretin (Prealbumin) in Dialysis Patients
- Protein Status in Pancreatitis – Transthyretin Is a Sensitive Biomarker of Malnutrition in Acute and Chronic Pancreatitis
- Assessment of Nutritional Status in Organ Transplant: Is Transthyretin a Reliable Indicator?
- Body Composition and Nutritional Parameters in HIV and AIDS Patients
- C-Reactive Protein to Transthyretin Ratio for the Early Diagnosis and Follow-up of Postoperative Infection
- The Prognostic Value of Nutritional and Inflammatory Indices in Critically Ill Patients with Acute Respiratory Failure
- Transthyretin: Its Response to Malnutrition and Stress Injury. Clinical Usefulness and Economic Implications
- Transthyretin Measurement as a Screening Tool for Protein Calorie Malnutrition in Emergency Hospital Admissions
- Outcomes of Continuous Process Improvement of a Nutritional Care Program Incorporating TTR Measurement
- The Role of Visceral Protein Markers in Protein Calorie Malnutrition
- Acknowledgement
- Meetings
