Synthesis Of Transthyretin Research Articles

Transthyretin expression in medulloblastomas and medulloblastoma cell lines

Transthyretin is a protein crucial to the transport of lipophilic molecules such as thyroid hormones and retinoids. In the central nervous system, large amounts of transthyretin are synthesized by the choroid plexus and are secreted into the cerebrospinal fluid. The choroid plexus is the only site of transthyretin synthesis in the brain. Transthyretin is expressed by most benign and malignant choroid plexus tumours while gliomas and meningiomas do not express transthyretin. Other major sites of transthyretin synthesis are the retinal pigment epithelium and hepatocytes. Medulloblastoma is the prototypical primitive neuroectodermal tumour of the cerebellum and can show multiple lines of differentiation, including the expression of retinal markers. In this study, we examined transthyretin expression both at the RNA and protein level in four medulloblastomas and six medulloblastoma cell lines using Northern and Western blot analysis, reverse transcription polymerase chain reaction (PCR), RNA in situ hybridization, and immunohistochemistry. All four medulloblastomas and five of the six medulloblastoma cell lines expressed transthyretin-mRNA as demonstrated by reverse PCR and in situ hybridization while three medulloblastomas and one cell line were positive on Northern blot. The medulloblastoma with the most abundant RNA expression was transthyretin-immunoreactive on cryosections and the medulloblastoma cell line that was positive on Northern blot also expressed transthyretin at levels detectable by Western blot. No transthyretin-immunoreactivity was seen in 16 additional medulloblastomas studied on paraffin sections. These findings indicate that low-level expression of transthyretin-mRNA is common in medulloblastomas and medulloblastoma cell lines. Expression of transthyretin protein occurs rarely but can reach significant levels. Transthyretin expression in medulloblastoma is consistent with retinal pigment epithelium differentiation in medulloblastomas and reflects their pluripotential nature. Furthermore, the potential for transthyretin-immunoreactivity in medulloblastoma should be kept in mind when performing immunohistochemical studies on poorly differentiated cerebellar tumours.

Evolution of transthyretin in marsupials.

The evolution of the expression and the structure of the gene for transthyretin, a thyroxine-binding plasma protein formerly called prealbumin, was studied in three marsupial species: the South American polyprotodont Monodelphis domestica, the Australian polyprotodont Sminthopsis macroura and the Australian diprotodont Petaurus breviceps. The transthyretin gene was found to be expressed in the choroid plexus of all three species. In liver it was expressed in P. breviceps and in M. domestica, but not in S. macroura. This, together with previous studies [Richardson, S. J., Bradley, A. J., Duan, W., Wettenhall, R. E. H., Harms, P. J., Babon, J. J., Southwell, B. R., Nicol, S., Donnellan, S. C. & Schreiber, G. (1994) Am. J. Physiol. 266, R1359-R1370], suggests the independent evolution of transthyretin synthesis in the liver of the American Polyprotodonta and the Australian Diprotodonta. The results obtained from cloning and sequencing of the cDNA for transthyretin from the three species suggested that, in the evolution of the structure of transthyretin in vertebrates, marsupial transthyretin structures are intermediate between bird/reptile and eutherian transthyretin structures. In marsupials, as in birds and reptiles, a hydrophobic tripeptide beginning with valine and ending with histidine was found in transthyretin at a position which has been identified in eutherians as the border between exon 1 and intron 1. In humans, rats and mice, the nine nucleotides, coding for this tripeptide in marsupials/reptiles/birds, are found at the 5' end of intron 1. They are no longer present in mature transthyretin mRNA. This results in a change in character of the N-termini of the subunits of transthyretin from hydrophobic to hydrophilic. This change might affect the accessibility of the thyroxine-binding site in the central channel of transthyretin, since, at least in humans, the N-termini of the subunits of transthyretin are located in the vicinity of the channel entrance [Hamilton, J. A., Steinrauf, L. K., Braden, B. C., Liepnieks, J., Benson, M. D., Holmgren, G., Sandgren, O. & Steen, L. (1993) J. Biol. Chem. 268, 2416-2424].

Evolution of marsupial and other vertebrate thyroxine-binding plasma proteins

Binding of radioactive thyroxine to proteins in the plasma of vertebrates was studied by electrophoresis followed by autoradiography. Albumin was found to be a thyroxine carrier in the blood of all studied fish, amphibians, reptiles, monotremes, marsupials, eutherians (placental mammals), and birds. Thyroxine binding to transthyretin was detected in the blood of eutherians, diprotodont marsupials, and birds, but not in blood from fish, toads, reptiles, monotremes, and Australian polyprotodont marsupials. Globulins binding thyroxine were only observed in the plasma of some mammals. Apparently, albumin is the phylogenetically oldest thyroxine carrier in vertebrate blood. Transthyretin gene expression in the liver developed in parallel, and independently, in the evolutionary lineages leading to eutherians, to diprotodont marsupials, and to birds. In contrast, high transthyretin mRNA levels, strong synthesis, and secretion of transthyretin in choroid plexus from reptiles and birds indicate that transthyretin gene expression in the choroid plexus evolved much earlier than in the liver, probably at the stage of the stem reptiles. NH2-terminal sequence analysis suggests a change of transthyretin pre-mRNA splicing during evolution.

Synthesis and secretion of retinol-binding protein and transthyretin by cultured retinal pigment epithelium

Recent studies indicate that the retinal pigment epithelium (RPE) may serve as an extrahepatic source of retinol-binding protein (RBP) and transthyretin (TTR) for the retina by virtue of the fact that this cell layer is the exclusive retinal location for mRNA coding for these proteins [Herbert, J., et al. (1991) Invest. Ophthalmol. Vis. Sci. 32, 302-309; Cavallaro, T., et al. (1990) Invest. Ophthalmol. Vis. Sci. 31, 497-501], although the proteins themselves are present in a variety of retinal neurons. It is therefore necessary to determine whether these mRNAs are translated and whether their translated products are secreted like hepatic RBP and TTR. Metabolic labeling of cultured bovine RPE with [35S]cysteine and [35S]methionine and subsequent analysis of newly synthesized proteins in the conditioned medium by affinity chromatography, gel filtration, partial amino acid sequence analysis, and autoradiography of electrophoretograms indicate that both RBP and TTR are synthesized and secreted by the RPE. Moreover, for cells grown in chambers with permeable supports, the predominant direction for secretion was into the apical medium. The mean apical:basal ratio after 72 h of incubation was 9.2 for TTR and 4.5 for RBP. A function for these proteins in the neurosensory retina remains speculative. They could be involved in the delivery of all-trans-retinol to amacrine and Müller cells as a precursor for retinoic acid, since these cells are known to contain cellular retinoic acid binding protein [Gaur, V.P., et al. (1990) Exp. Eye Res. 50, 505-511; Milam et al. (1990) J. Comp. Neurol. 296, 123-129].(ABSTRACT TRUNCATED AT 250 WORDS)

Thyroxine transport to the brain: role of protein synthesis by the choroid plexus

A cell culture model for the blood-cerebrospinal fluid barrier in choroid plexus was developed. The relationship between synthesis and secretion of transthyretin across a layer of epithelial cells derived from rat choroid plexus and the transport of T4 was analyzed in a two-chamber system. Choroid plexus cells were dispersed and placed on a porous filter suspended in cell culture medium. A monolayer of polarized epithelial cells developed after 5 days in culture, separating fluid in the upper (apical) chamber from fluid in the lower (basal) chamber. Electrical resistance across the cell layer was 100 Ohm/cm2. Transthyretin was synthesized and secreted by these cells. Over 32 h, transthyretin accumulated in the fluid in the apical chamber to twice the concentration in the basal chamber. [125I]T4 added to the basal chamber permeated to the apical fluid and accumulated in the apical chamber to twice the concentration in the basal fluid. Upon inhibition of protein synthesis, T4 equilibrated to a similar concentration in the two chambers. Thus, the accumulation of T4 in the apical chamber required continuing protein synthesis. Competitive inhibition of T4 binding to transthyretin by EMD 21388 also prevented the accumulation of T4 to a higher concentration in the upper than in the lower chamber. These data suggest that T4 partitions through the choroid plexus and that transthyretin synthesis and secretion by the choroid plexus determines the concentration of T4 in the apical fluid. A model is proposed for the involvement of transthyretin secreted by the choroid plexus, in the in vivo distribution of T4 in the brain.

Thyroxine transport to the brain: role of protein synthesis by the choroid plexus.

A cell culture model for the blood-cerebrospinal fluid barrier in choroid plexus was developed. The relationship between synthesis and secretion of transthyretin across a layer of epithelial cells derived from rat choroid plexus and the transport of T4 was analyzed in a two-chamber system. Choroid plexus cells were dispersed and placed on a porous filter suspended in cell culture medium. A monolayer of polarized epithelial cells developed after 5 days in culture, separating fluid in the upper (apical) chamber from fluid in the lower (basal) chamber. Electrical resistance across the cell layer was 100 Ohm/cm2. Transthyretin was synthesized and secreted by these cells. Over 32 h, transthyretin accumulated in the fluid in the apical chamber to twice the concentration in the basal chamber. [125I]T4 added to the basal chamber permeated to the apical fluid and accumulated in the apical chamber to twice the concentration in the basal fluid. Upon inhibition of protein synthesis, T4 equilibrated to a similar concentration in the two chambers. Thus, the accumulation of T4 in the apical chamber required continuing protein synthesis. Competitive inhibition of T4 binding to transthyretin by EMD 21388 also prevented the accumulation of T4 to a higher concentration in the upper than in the lower chamber. These data suggest that T4 partitions through the choroid plexus and that transthyretin synthesis and secretion by the choroid plexus determines the concentration of T4 in the apical fluid. A model is proposed for the involvement of transthyretin secreted by the choroid plexus, in the in vivo distribution of T4 in the brain.

Transthyretin expression evolved more recently in liver than in brain

1. 1. Transthyretin was found to be synthesized and secreted by choroid plexus from rats, echidnas, and lizards, but not toads. 2. 2. Transthyretin was observed in blood from placental mammals, birds, and marsupials, but not reptiles and monotremes. 3. 3. The obtained data suggest that transthyretin synthesis by the liver evolved independently in the lineage leading to the placental mammals and marsupials and in that leading to the birds. 4. 4. It is proposed that transthyretin gene expression in mammalian liver appeared about 200 million years later than its first occurrence in the choroid plexus of the stem reptiles.

The Expression of the Transthyretin Gene in Liver Evolved during the Radiation of Diprotodont Marsupials in Australia

Thyroid hormone-binding proteins in blood plasma were identified in 28 different marsupial species by their capacity to bind radioactive thyroxine. All species contained albumin. Transthyretin was not found in the blood from any of 12 polyprotodont marsupial species, but was abundant in the blood from all of 16 diprotodont marsupial species investigated. Transthyretin mRNA was absent from the liver of the stripe-faced dunnart, a polyprotodont marsupial, but abundant in the liver of the diprotodont grey kangaroo. Diprotodont marsupials probably evolved in Australia from polyprotodont marsupials after their transantarctic migration from South America, about 40 million years ago. It is suggested that hepatic transthyretin expression evolved in marsupials during the radiation of herbivorous, diprotodont species in Australia. The earlier appearance of transthyretin gene expression in the choroid plexus of the stem reptiles, about 300 million years ago, contrasts with hepatic transthyretin synthesis, a relatively late evolutionary event, occurring independently in at least three lineages.

Protein synthesis at the blood-brain barrier. The major protein secreted by amphibian choroid plexus is a lipocalin

Among the proteins secreted by choroid plexus of vertebrates, one protein is much more abundant than all others. In mammals, birds, and reptiles this protein is transthyretin, a tetramer of identical 15-kDa subunits. In this study choroid plexus from frogs, tadpoles, and toads incubated in vitro were found to synthesize and secrete one predominant protein. However, this consisted of one single 20-kDa polypeptide chain. It was expressed throughout amphibian metamorphosis. Part of its amino acid sequence was determined and used for construction of oligonucleotides for polymerase chain reaction. The amplified DNA was used to screen a toad choroid plexus cDNA library. Full-length cDNA clones were isolated and sequenced. The derived amino acid sequence for the encoded protein was 183 amino acids long, including a 20-amino acid presegment. The calculated molecular weight of the mature protein was 18,500. Sequence comparison with other proteins showed that the protein belonged to the lipocalin superfamily. Its expression was highest in choroid plexus, much lower in other brain areas, and absent from liver. Since no transthyretin was detected in proteins secreted from amphibian choroid plexus, abundant synthesis and secretion of transthyretin in choroid plexus must have evolved only after the stage of the amphibians.

Studies on the synthesis and secretion of transthyretin by the human hepatoma cell line Hep G2

Transthyretin (TTR) is a circulatory protein which plays an important role in the transport of both thyroid hormone and retinol. Hep G2 cells, a human hepatoma-denved cell line. have been used extensively in studies of protein secretion by liver cells. The original description of this cell line indicated that this line, unlike primary hepatocytes, does not secrete TTR. We now report studies which reexamine the ability of Hep G2 cells to synthesize and secrete TTR. For this purpose, total RNA was isolated from Hep G2 cells grown on both uncoated and collagen-coated plastic plates and was examined for TTR expression by Northern blot analysis. TTR mRNA was found to be present m nearly equal amounts in Hep G2 cells cultured in either condition. When Hep G2 cells were cultured in [ 35S]jmethionine-containing medium, the cells were found both to synthesize and to secrete immunoprecipitable [ 35S]SJTTR. Hep G2 cells were found, by sensitive and specific radioimmunoassay, to contain 142 ± 91 ng TTR/10 6 cells and to secrete TTR into the medium at a nearly constant rate for at least 24 h after medium change. Our data demonstrate that Hep G2 cells do synthesize and secrete TTR and suggest that this cell line might be useful for studies of the secretion of TTR.

A sensitive assay of transthyretin (prealbumin) in human cerebrospinal fluid in nanogram amounts by ELISA

A sensitive ELISA method for determining transthyretin (prealbumin) in human cerebrospinal fluid (CSF) is described. The method utilizes goat antihuman transthyretin antibody (IgG fraction) for capture and peroxidase conjugated antibody for color development. The assay has a linear range of 1–4 ng transthyretin added per well. The within-day and between-day coefficients of variation are 5.1 and 6.1%, respectively. The concentration of transthyretin in CSF (ranging from 5 to 20 mg per L) correlated significantly with the corresponding serum concentrations (range 170–420 mg/l). This suggests that synthesis of transthyretin in the brain and peripheral tissues is under similar biological control in normal subjects. The transthyretin concentrations in CSF did not correlate with total CSF protein concentration or age of the subject.

Transthyretin (prealbumin) gene expression in choroid plexus is strongly conserved during evolution of vertebrates

1. 1. The major protein synthesized and secreted by the choroid plexus from mammals, birds, reptiles and probably amphibians is similar in subunit structure to transthyretin. 2. 2. In mammals and birds the proportion of transthyretin mRNA is much higher in choroid plexus RNA than in liver RNA. No transthyretin mRNA is found in brain outside the choroid plexus. 3. 3. Transthyretin-like protein, such as that secreted by the choroid plexus, was not detected in amphibian serum and was present in very low levels in reptile serum. 4. 4. It is proposed that transthyretin synthesis and secretion arose earlier in evolution in the choroid plexus than in the liver.

Thyroxine transport from blood to brain via transthyretin synthesis in choroid plexus

The transport of thyroxine from the bloodstream to the brain and the synthesis and secretion of transthyretin (formerly called prealbumin) were studied in rats and in sheep choroid plexus perfused in vitro. Rat choroid plexus contained 4.4 micrograms and rat liver 0.39 micrograms transthyretin mRNA per gram wet tissue. The specific radioactivity of transthyretin isolated from cerebrospinal fluid of rats 60 min after intravenous injection of [14C]leucine was greater than 50 times that of transthyretin from serum. After adding [14C]leucine to the perfusion medium of an in vitro perfused sheep choroid plexus, highly radioactive transthyretin was isolated from freshly secreted cerebrospinal fluid collected from the exposed choroid plexus surface. Secretion of newly synthesized transthyretin into the perfusion medium could not be demonstrated. After intravenous injection of [125I]-thyroxine into rats, a maximum in the curve of radioactivity in tissue plotted against time after injection was observed first for choroid plexus, thereafter for cerebrospinal fluid, and still later for cortex and striatum. Based on the obtained data, a hypothesis is derived for the mechanism of the transport of thyroid hormones from the bloodstream to the brain involving transthyretin synthesized in choroid plexus and secreted into the cerebrospinal fluid.

Thyroxine transport in choroid plexus.

The role of the choroid plexus in thyroid hormone transport between body and brain, suggested by strong synthesis and secretion of transthyretin in this tissue, was investigated in in vitro and in vivo systems. Rat choroid plexus pieces incubated in vitro were found to accumulate thyroid hormones from surrounding medium in a non-saturable process. At equilibrium, the ratio of thyroid hormone concentration in choroid plexus pieces to that in medium decreased upon increasing the concentration of transthyretin in the medium. Fluorescence quenching of fluorophores located at different depths in liposome membranes showed maximal hormone accumulation in the middle of the phospholipid bilayer. Partition coefficients of thyroxine and triiodothyronine between lipid and aqueous phase were about 20,000. After intravenous injection of 125I-labeled thyroid hormones, choroid plexus and parts of the brain steadily accumulated 125I-thyroxine, but not [125I]triiodothyronine, for many hours. The accumulation of 125I-thyroxine in choroid plexus preceded that in brain. The amount of 125I-thyroxine in non-brain tissues and the [125I]triiodothyronine content of all tissues decreased steadily beginning immediately after injection. A model is proposed for thyroxine transport from the bloodstream into cerebrospinal fluid based on partitioning of thyroxine between choroid plexus and surrounding fluids and binding of thyroxine to transthyretin newly synthesized and secreted by choroid plexus.

Synthesis of Retinol-binding Protein and Transthyretin in Yolk Sac and Fetus in the Rat

Levels of retinol-binding protein (RBP) and transthyretin (TTR) were determined in rat maternal livers, placenta, yolk sac, whole fetuses and fetal livers at different stages of gestation. Yolk sac concentrations of RBP and TTR expressed as micrograms per mg protein were three- to fivefold higher than liver values. TTR (moles) in the whole fetus was higher than RBP at all stages of gestation. Fetal hepatic RBP concentration was relatively constant throughout gestation, where fetal hepatic TTR concentration was low until close to parturition. RBP was observed in fetal microsomes at 12 d gestation. Incorporation of labeled amino acids into both RBP and TTR in vitro was observed in the yolk sac. In the 20-d fetal liver, incorporation to RBP and TTR was observed, whereas at 14 d gestation, incorporation only to RBP was observed. A small amount of synthesis of both proteins was also observed in the placenta. In the fetal circulation at 20–21 d gestation, no TTR-RBP complex was observed; instead a broad peak of RBP was found eluting at 20,000–40,000 daltons on gel chromatography. Incubation of fetal serum with maternal TTR resulted in an RBP peak eluting with an Mr of approximately 40,000. Treatment of the fetal serum with either lysozyme, neuraminidase or endoglycosidase H resulted in a 20,000 dalton RBP peak and following incubation with maternal TTR, a 70,000 dalton RBP-TTR complex was formed. Yolk sac, fetal liver and amniotic fluid on gel filtration exhibited a 40,000–20,000 dalton RBP peak. It is suggested that retinol transport in the fetus may involve RBP and TTR synthesized in the yolk sac as well as in fetal tissue. Results obtained after glycosidase treatment suggest that RBP or TTR in the fetus may be glycosylated and thus differ from the adult proteins.

Retinol-binding protein and transthyretin mRNA levels in visceral yolk sac and liver during fetal development in the rat.

Studies were conducted to explore the synthesis of retinol-binding protein and transthyretin by embryonic and extraembryonic tissues during fetal development in the rat. The levels of retinol-binding protein mRNA and transthyretin mRNA were measured in fetal liver and in extraembryonic tissues by RNA gel blot analysis and hybridization with specific cDNA probes. Retinol-binding protein mRNA and transthyretin mRNA were both detected in the liver of fetuses at 14 days of gestation. The relative levels of these two transcripts increased during later fetal development; by the 20th day of gestation retinol-binding protein mRNA levels were comparable to those of the adult liver, while the levels of transthyretin mRNA were only 46% of those of the adult liver. Examination of the extraembryonic membranes for retinol-binding protein mRNA and transthyretin mRNA showed that these two transcripts were present specifically and only in the visceral yolk sac. The relative levels of retinol-binding protein mRNA and transthyretin mRNA in visceral yolk sac were constant from 14 to 20 days of gestation, averaging 58% and 51%, respectively, of the adult liver levels of these two transcripts. Both retinol-binding protein mRNA and transthyretin mRNA in the visceral yolk sac were found to be specifically localized in the endodermal layer. Finally, both immunoprecipitable retinol-binding protein and transthyretin were found to be synthesized and secreted by explant cultures of visceral yolk sac tissue. These data show that the visceral yolk sac is a major source of both retinol-binding protein and transthyretin in the developing fetus. Since the visceral yolk sac is a site of true placentation and nutrient transfer in the rodent, this raises the possibility that visceral yolk sac-derived retinol-binding protein and transthyretin may play important roles in the transport and delivery of retinol from the maternal blood to the developing fetus.

Synthesis of transthyretin (pre-albumin) mRNA in choroid plexus epithelial cells, localized by in situ hybridization in rat brain.

The sites of synthesis of transthyretin in the brain were investigated using in situ hybridization with [35S]-labeled recombinant cDNA probes specific for transthyretin mRNA. Autoradiography of hybridized coronal sections of rat brain revealed specific cellular localization of transthyretin mRNA in choroid plexus epithelial cells of the lateral, third, and fourth ventricles. Transferrin mRNA was also investigated and, in contrast to transthyretin mRNA, was localized mainly in the lateral ventricles. Our results indicate that substantial synthesis of transthyretin and transferrin mRNA may occur in the choroid plexus.

High levels of messenger RNA for transthyretin (prealbumin) in human choroid plexus

We have investigated the expression of the gene for transthyretin (prealbumin) in the human choroid plexus. RNA was isolated from the human choroid plexus, fractionated by electrophoresis in agarose gel and transferred onto a nitrocellulose filter membrane. Transthyretin messenger RNA (mRNA) was identified by hybridization to radioactive complementary DNA for rat transthyretin. The level of transthyretin mRNA in the human choroid plexus was found to be at least 40 times higher than in human liver, suggesting very active synthesis of transthyretin in the choroid plexus.

Rat choroid plexus specializes in the synthesis and the secretion of transthyretin (prealbumin). Regulation of transthyretin synthesis in choroid plexus is independent from that in liver.

Synthesis of total protein and of transthyretin in rat choroid plexus was studied by measuring the incorporation of radioactive leucine into proteins in choroid plexus tissue incubated in vitro. About 20% of the protein newly synthesized in choroid plexus and about 50% of the newly synthesized protein secreted into the medium was transthyretin. Evidently, the choroid plexus is very active in the biosynthesis of this carrier protein for thyroid hormones and could be an important link in the chemical communication between the body and the central nervous system. Acute inflammation, which leads to a profound rearrangement of the pattern of plasma protein synthesis rates in the liver, produced distinct changes in the levels for plasma protein mRNAs in the liver. The levels of the mRNAs for alpha 1-acid glycoprotein and major acute phase alpha 1-protein increased more than 30-fold, those for transthyretin and albumin decreased to 27 and 57% of normal, respectively. The pattern of the observed changes in the levels of mRNAs for plasma proteins in the liver was independent of whether the acute inflammation was produced by subcutaneous injection of turpentine or intraperitoneal injection of a suspension of talcum. However, levels of transthyretin mRNA in choroid plexus were affected only very slightly, or not at all. Apparently, transthyretin synthesis in liver and choroid plexus is regulated independently during the acute phase response. No mRNA was detected in choroid plexus for albumin, alpha 1-acid glycoprotein, and major acute phase alpha 1-protein under any conditions.

Rat transthyretin (prealbumin). Molecular cloning, nucleotide sequence, and gene expression in liver and brain.

Transthyretin cDNA was isolated from a rat liver cDNA library. Analysis of the nucleotide sequence revealed a signal peptide-like sequence preceding a section coding for a full length subunit and an untranslated sequence at the 3' end. The deduced primary structure of rat transthyretin was compared with that of human transthyretin. It was highly conserved at the binding sites for thyroxine and the interfaces and core regions of the subunits. The cDNA for transthyretin was used to measure mRNA levels by hybridization. During acute inflammation, the amount of transthyretin mRNA in liver decreased (reaching a minimum of 25% of the normal level 36 h after inducing inflammation), suggesting regulation of transthyretin synthesis at the mRNA level. Transthyretin mRNA was found only in the liver and in the choroid plexus, but not in other parts of the central nervous system nor in the adrenal glands, kidney, spleen, testes, heart, lung, intestine, and ovaries. One gram of choroid plexus contained about 25 times larger amounts of transthyretin mRNA than 1 g of liver. By synthesizing an important hormone carrier protein, the choroid plexus may be an important link in the chemical communication between the central nervous system and the bloodstream.