c-erb-A mRNA correlates with T3-receptor levels in liver and pituitary of tumor rats.
In the rat tumor model of the sick euthyroid syndrome, differential regulation of T3-induced cellular responses have been demonstrated in liver and anterior pituitary. These effects occur with a concomitant decrease in nuclear thyroid hormone receptor (TR) number as measured by the binding of 125I-labeled T3. To explore the possibility that these altered responses to T3 in tumor rats resulted from changes in the expression of different TR forms, we correlated the relative abundance of mRNAs encoding each receptor form with the concentration of TR measured by specific T3 binding. In anterior pituitary of tumor rats, TR beta-1 and beta-2 mRNA levels decreased to 51 and 45%, respectively, compared to controls; rat c-erb A alpha-2 mRNA, which encodes a TR-related DNA alpha-binding protein that does not bind T3, decreased to 46% of control. These findings correlate with a decrease in nuclear T3 binding capacity that has been shown to be 63% of control. The level of TR beta-1 mRNA, the only quantifiable TR form in liver, was decreased to 61% of control in the same hepatic tissue that revealed a 50% decrease in TR as measured by specific T3 binding. The coordinate down-regulation of all TR mRNA forms to a degree that parallels the decrease in TR number as measured by specific T3 binding suggests that the differential regulation of T3-mediated effects in illness is by a mechanism other than changing concentrations of specific receptor forms.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Medicine, Montefiore Medical Center, Bronx, New York.
K H
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Hupart
R A
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Hodin
M A
MA
Lazar
L E
LE
Shapiro
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Chin
M I
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Surks
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D009374:Neoplasms, Experimental / Q000235:genetics* / Q000378:metabolism; D010903:Pituitary Gland, Anterior / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011988:Receptors, Thyroid Hormone / Q000378:metabolism*; D014284:Triiodothyronine / Q000378:metabolism
D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D011988:Receptors, Thyroid Hormone; D014284:Triiodothyronine