title: Transport of L-[125I]thyroxine by in situ perfused ovine choroid plexus: inhibition by lead exposure.
abstract: Lead (Pb) exposure hinders brain development in children by mechanisms that remain unknown. Previous evidence shows that sequestration of Pb in the choroid plexus lowers the production and secretion of transthyretin (TTR), a thyroxine (T4) transport protein, from the choroid plexus into the cerebrospinal fluid (CSF). This study was undertaken to characterize the uptake kinetics of T4 by the choroid plexus and to determine if in vivo Pb exposure altered the T4 uptake in an in situ perfused ovine choroid plexus model. Sheep received i.p. injections of Pb acetate (20 mg Pb/kg) or Na acetate (as the controls) every 48 h for a period of 16 d. The [125I]T4 uptake was determined by a paired-tracer perfusion method using 0.5 microCi [125I]T4 and 2 microCi [14C]mannitol at various concentrations of unlabeled T4 (trace to 20 microM). The flux of [125I]T4 into the choroid plexus followed Michaelis-Menten kinetics with the maximum flux (Vmax) of 56.6 nmol/min/g and half-saturation constant (Km) of 10.7 mumol/L, suggesting an evident saturable influx of T4 into the choroid epithelium. In vivo Pb exposure in these sheep resulted in a significant accumulation of Pb in the choroid plexus and hippocampus. Pb treatment diminished the Vmax by 63.7% of control, but did not alter Km. The maximal cellular uptake (Umax) and net uptake (Unet) in Pb-treated animals were 2.1-fold and 1.9-fold, respectively, lower than those of control. Exposure to Pb, however, did not significantly change the flow rate through the choroid plexus. Data suggest that the choroid plexus may serve as a significant site for T4 transport into the CSF, and Pb exposure may hinder the influx of T4 from the blood into the choroid plexus.
authors.affiliation: Department of Environmental Health Sciences, School of Public Health, Columbia University, New York, New York, USA. wz18@Columbia.edu
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
authors.forename: Rashid
authors.initials: R
authors.lastname: Deane
authors.forename: Zoran
authors.initials: Z
authors.lastname: Redzic
authors.forename: Jane E
authors.initials: JE
authors.lastname: Preston
authors.forename: Malcolm B
authors.initials: MB
authors.lastname: Segal
mesh_terms: D000818:Animals; D002831:Choroid Plexus / Q000502:physiology*; D004195:Disease Models, Animal; D007274:Injections, Intraperitoneal; D007457:Iodine Radioisotopes; D007700:Kinetics; D007854:Lead / Q000008:administration & dosage / Q000009:adverse effects*; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000009:adverse effects*; D012756:Sheep; D013974:Thyroxine / Q000493:pharmacokinetics*
chemical_list: D007457:Iodine Radioisotopes; D009942:Organometallic Compounds; D007854:Lead; D013974:Thyroxine; C008261:lead acetate