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

Abstract

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.