TRβ1 protein is preferentially expressed in the pericentral zone of rat liver and exhibits marked diurnal variation

Abstract

We investigated the distribution and diurnal variation of TRβ1 protein expression in liver with specific antibodies against TRβ1. Immunohistochemistry showed a zonal distribution of TRβ1 with maximum expression in the pericentral zone matching some known T3-responsive enzyme activities in the liver, such as glutamine synthetase, cholesterol 7α-hydroxylase, and spot 14. Combining immunohistochemistry and image analysis we found and quantified the same zonal distribution for 5′-deiodinase type 1 as for TRβ1. Western blot analysis revealed a profound diurnal variation for TRβ1 protein expression, with highest levels at the beginning of the dark period. TRβ1 diurnal variation partly overlaps with the T3-responsive genes, cholesterol 7α-hydroxylase and spot 14. Furthermore, TRβ1 distribution along the porto-central axis does not change during the day, indicating that the zonal expression of TRβ1 is stable. This is the first time that zonal distribution in liver has been demonstrated for a member of the nuclear receptor family. This finding together with the observed diurnal rhythm has major implications for interpreting and timing experiments concerning the TR and its downstream actions in liver.