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Articles in PresS, published online ahead of print September 3, 2002
Am J Physiol Endocrinol Metab, 10.1152/ajpendo.00155.2002
Submitted on April 11, 2002
Accepted on August 28, 2002
1 Department of Veterans Affairs Medical Center, University of California, Metabolism Section, San Francisco, California, USA
* To whom correspondence should be addressed. E-mail: abeigneux{at}gladstone.ucsf.edu.
Infection is associated with low serum thyroid hormone and thyrotropin levels. Here we demonstrate that infection also reduces thyroid hormone receptor (TR) expression. In gel shift experiments, RXR/TR DNA binding was reduced in mouse liver by 60% and 77%, respectively 4 and 16 hours following lipopolysaccharide (LPS) administration. Surprisingly, LPS did not decrease either TR
or TRß protein levels at 4 hours, but by 16 hours TR1, TR2 and TRß levels were reduced by 55%, 87%, and 41% respectively. We previously reported that LPS rapidly decreases retinoid X receptor (RXR) protein levels in liver. Therefore, we added RXRß to hepatic nuclear extracts prepared 4 hours after LPS treatment, which restored RXR/TR DNA binding to a level comparable to that of controls. A similar experiment conducted on extracts prepared 16 hours following LPS administration did not restore RXR/TR DNA binding. We propose that decreased RXR expression is limiting for RXR/TR DNA binding at 4 hours, whereas the reduction in both TR and RXR levels results in further decreased binding at 16 hours.
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