TR 1 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 TR1 protein expression in liver with specific antibodies against TR1. Immunohistochemistry showed a zonal distri- bution of TR1 with maximum expression in the pericentral zone matching some known T3-responsive enzyme activities in the liver, such as glutamine synthetase, cholesterol 7- hydroxylase, and spot 14. Combining immunohistochemistry and image analysis we found and quantified the same zonal distribution for 5-deiodinase type 1 as for TR1. Western blot analysis revealed a profound diurnal variation for TR1 pro- tein expression, with highest levels at the beginning of the dark period. TR1 diurnal variation partly overlaps with the T3-responsive genes, cholesterol 7-hydroxylase and spot 14. Furthermore, TR1 distribution along the porto-central axis does not change during the day, indicating that the zonal expression of TR1 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. (En- docrinology 143: 979 -984, 2002)