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TRß1 Protein Is Preferentially Expressed in the Pericentral Zone of Rat Liver and Exhibits Marked Diurnal Variation

Departments of Endocrinology and Metabolism (B.Z.D., M.P.-T.S., H.C.v.B., E.F., O.B., W.M.W.) and Anatomy and Embryology (W.T.L., W.H.L.), Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands

Address all correspondence and requests for reprints to: Onno Bakker, Ph.D., Department of Endocrinology and Metabolism, F5-171, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. E-mail: . o.bakker{at}amc.uva.nl

We investigated the distribution and diurnal variation of TRß1 protein expression in liver with specific antibodies against TRß1. Immunohistochemistry showed a zonal distribution of TRß1 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 TRß1. Western blot analysis revealed a profound diurnal variation for TRß1 protein expression, with highest levels at the beginning of the dark period. TRß1 diurnal variation partly overlaps with the T₃-responsive genes, cholesterol 7-hydroxylase and spot 14. Furthermore, TRß1 distribution along the porto-central axis does not change during the day, indicating that the zonal expression of TRß1 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.

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