Molecular mechanisms of thyroid hormone action. A physiologic perspective.
At present, it appears abundantly clear that thyroid hormone exerts its major action at the nuclear level by regulating the level of mRNAs of specific genes. There are at least three TR isoforms that mediate hormonal effects at the tissue level. Characterization of the functional domains of these receptor isoforms is as yet incomplete, and the possibility that these receptors could have ligand-independent functions is a matter under current investigation. TRs are now recognized as members of a large superfamily of transactivating proteins involved in the regulation of gene expression. Recent studies have shown an unexpected degree of complexity in the nature of the association of the T3 receptors and the DNA of target genes. They have vividly pointed out the multiple interactions possible between the T3-receptor complex and other proteins participating in the process of gene regulation. These insights have provided a solid base for understanding differences in the gradation of thyroid hormone effect from one tissue to another. The microdissection of the molecular process that has occurred in the past 20 years has proceeded in part through the application of relatively artificial in vitro systems and assays. Whereas such approaches have undoubtedly reaped rich rewards in pointing out potential or possible mechanisms, they do not define the actual workings in the animal. Additional studies designed to examine at the molecular level the operation in vivo of physiologic networks influenced by thyroid hormones appear as an essential next step in understanding the biology of the hormone system. The application of transgenic models should materially assist such efforts.
Schwartz
H L
HL
Division of Endocrinology and Metabolism, School of Medicine, University of Minnesota, Minneapolis.
Strait
K A
KA
Oppenheimer
J H
JH
D000818:Animals; D001483:Base Sequence; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000235:genetics / Q000502:physiology*; D013963:Thyroid Hormones / Q000494:pharmacology*
D012333:RNA, Messenger; D011988:Receptors, Thyroid Hormone; D013963:Thyroid Hormones