Toxicological Sciences 61, 107-114 (2001)
Copyright © 2001 by the Society of Toxicology
NEUROTOXICOLOGY |
Transthyretin, Thyroxine, and Retinol-Binding Protein in Human Cerebrospinal Fluid: Effect of Lead Exposure
,1
* Division of Environmental Health Sciences, School of Public Health,
Departments of Pharmacology and
§ Medicine, College of Physicians and Surgeons, Columbia University, New York, New York 10032; and
Department of Neurosurgery, Hangzhou First Hospital, Hangzhou, Zhejiang 310006, People's Republic of China
Transthyretin (TTR), synthesized by the choroid plexus, is proposed to have a role in transport of thyroid hormones in the brain. Our previous studies in animals suggest that sequestration of lead (Pb) in the choroid plexus may lead to a marked decrease in TTR levels in the cerebrospinal fluid (CSF). The objectives of this study were to establish in humans whether TTR and thyroxine (T4) are correlated in the CSF, and whether CSF levels of Pb are associated with those of TTR, T4, and/or retinol-binding protein (RBP). Eighty-two paired CSF and blood/serum samples were collected from patients undergoing clinical diagnosis of CSF chemistry. Results showed that the mean value of CSF concentrations for TTR was 3.33 ± 1.60 µg/mg of CSF proteins (mean ± SD, n = 82), for total T4 (TT4) was 1.56 ± 1.68 ng/mg (n = 82), for RBP was 0.34 ± 0.19 µg/mg (n = 82), and for Pb was 0.53 ± 0.69 µg/dl (n = 61 for those above the detection limit). Linear regression analyses revealed that CSF TTR levels were positively associated with those of CSF TT4 (r = 0.33, p < 0.005). CSF TTR concentrations, however, were inversely associated with CSF Pb concentrations (r = –0.29, p < 0.05). There was an inverse, albeit weak, correlation between CSF TT4 and CSF Pb concentrations (r = –0.22, p = 0.09). The concentrations of TTR, TT4, and Pb in the CSF did not vary as the function of their levels in blood or serum, but RBP concentrations in the CSF did correlate to those of serum (r = 0.39, p < 0.0005). Unlike TTR, CSF RBP concentrations were not influenced by Pb. These human data are consistent with our earlier observations in animals, which suggest that TTR is required for thyroxine transport in the CSF and that Pb exposure is likely associated with diminished TTR levels in the CSF.
Key Words: transthyretin; thyroxine; retinol-binding protein; lead; cerebrospinal fluid; choroid plexus.
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