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Department of Medicine, University of California San Francisco and Metabolism Section, Medical Service, Department of Veterans Affairs Medical Center, San Francisco, California 94121
Infection is associated
with low serum thyroid hormones and thyrotropin levels. Here we
demonstrate that infection also reduces thyroid hormone receptor (TR)
expression. In gel shift experiments, retinoid X receptor (RXR)/TR DNA
binding was reduced in mouse liver by 60 and 77%, respectively, 4 and
16 h after lipopolysaccharide (LPS) administration. Surprisingly,
LPS did not decrease either TR-
or TR-
protein levels at 4 h, but by 16 h TR-1, TR-2, and
TR- levels were reduced by 55, 87, and 41%, respectively. We
previously reported that LPS rapidly decreases RXR protein levels in
liver. Therefore, we added RXR- to hepatic nuclear extracts prepared
4 h 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 h after LPS administration did
not restore RXR/TR DNA binding. We propose that decreased RXR expression is limiting for RXR/TR DNA binding at
4 h, whereas the reduction in both TR and RXR levels results in
further decreased binding at 16 h.
acute-phase response; thyroid hormone receptor; retinoid X receptor; lipid metabolism
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