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 β-1 and β-2 mRNA levels decreased to 51 and 45%, respectively, compared to controls; rat c-erb A α-2 mRNA, which encodes a TR-related DNA α-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 β-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. Additionally, the parallel regulation of TR β mRNAs in the tumor rat contrasts with the opposing regulation of these species with other manipulations, suggesting a novel mode of regulation of the TR.