Interaction of thyroid hormones with target tissues: effects of hepatic mRNA population.

: Although the molecular basis of thyroid hormone action remains obscure, a growing body of evidence has suggested that triiodothyronine (T3) action is initiated at a set of specific nuclear receptor sites. The physiologic significance of these T3-binding sites is supported by four lines of evidence: 1) the high-affinity, limited-capacity binding of T3; 2) the relationship between binding affinity of thyroid hormone analogs and hormonal potency; 3) the correlation of concentration of nuclear receptor and physiologic response in various tissues; 4) the relationship between receptor occupancy and physiologic response. While the levels of hepatic nuclear receptor do not change in response to T3, recent evidence indicates receptor concentration is markedly reduced by partial hepatectomy, starvation, or administration of glucagon. This reduction results in a decrease in the response of malic enzyme to T3, but leaves the response of alpha-glycerol phosphate dehydrogenase unimpaired. Thus, specific control of thyroid responses by modulating receptor concentration may occur. Occupancy of hepatic receptors by T3 is associated with increases in both the rate of formation and steady-state concentration of poly(A)-containing mRNA. The values of these two parameters in the euthyroid rat liver were approximately 60--80% greater than values in hypothyroid animals. Analyses of the sequence and frequency complexity of poly(A)-containing mRNA from euthyroid and hypothyroid rats revealed no major changes in either the qualitative or quantitative distribution of mRNA sequences. Although it is recognized that the levels of certain specific species of mRNA (ie, alpha 2u-globulin) are altered as a result of thyroid hormone action, these data strongly indicate a concomitant generalized increase in the production of all major classes of mRNA.