Relationship of c-erbA mRNA content to tissue triiodothyronine nuclear binding capacity and function in developing...

We have quantitated in adult and developing rat tissues the molar concentrations of c-erbA alpha 1- and beta 1-mRNAs, which code for nuclear T3-binding proteins, and c-erbA alpha 2-mRNA, which is generated by alternate splicing of the alpha gene transcript and codes for a receptor variant that does not bind T3. Comparison of the concentrations of c-erbA alpha 1-mRNA, beta 1-mRNA, or their sum to the T3 nuclear binding capacity per mg of DNA in adult liver, kidney, heart, cerebrum, and cerebellum and during the ontogeny of liver and brain shows that the T3 binding capacity/c-erbA mRNA ratio is tissue-specific and related to developmental state. Administration of T3 resulted in a 40-50% fall in the alpha 1 signal of adult liver, kidney, and heart without changing either the beta 1 signal or T3 binding capacity. A 40-fold increase in rat brain beta 1-mRNA occurred in the transition between the 19-day gestational fetus and the 10-day-old neonate. This corresponds to the period during which the T3 content rises in brain and during which T3 is known to influence central nervous system development. Our findings indicate that important translational or post-translational factors influence nuclear binding capacity and raise the possibility that c-erbA beta 1 may play a primary role in mediating T3 effects in developing and adult animals.