Biomaterial Database

Physiology of the steroid-thyroid hormone nuclear receptor superfamily. 1994

G R Williams, and J A Franklyn

Department of Medicine, Queen Elizabeth Hospital, University of Birmingham, Edgbaston, UK.

Glucocorticoids, other steroid hormones, thyroid hormones and vitamin-derived hormones (including retinoids) all exert their effects by the regulation of hormone-responsive target genes within the cell nucleus. These hormones bind to a series of specific nuclear receptor proteins that function as hormone-inducible transcription factors. The receptors are structurally homologous, are related to the avian erythroblastosis oncogene v-erbA, and exhibit remarkable evolutionary conservation. Together they form the steroid-thyroid hormone nuclear receptor superfamily. This chapter describes the structure and functions of the various family members and highlights the differences and similarities that occur between individual receptor proteins. Type I receptors, which include glucocorticoid receptor and other steroid receptor proteins, interact as homodimers with target sequences of DNA containing two receptor binding sites arranged as a palindrome. Type II receptors, which include receptors for retinoids, thyroid hormone and vitamin D3, bind as heterodimers (or homodimers) to DNA sequences in which two or more receptor-binding sites are arranged as a direct repeat or as other more complex configurations. The complexity of both receptor-DNA and receptor-receptor interactions predicts the potential for considerable cross-talk between various hormone-activated pathways. Thus, the specificity of hormone action and its regulation is discussed in relation to the structural and functional characteristics of the receptors and their molecular mechanisms of action. Finally, potential sites of regulation of hormone action, from circulating hormone levels in the periphery to their delivery to the cell and final site of action in the nucleus, are highlighted to provide a perspective for the following chapters in this volume and to indicate their clinical significance.

UI	MeSH Term	Description	Entries
D011987	Receptors, Steroid	Proteins found usually in the cytoplasm or nucleus that specifically bind steroid hormones and trigger changes influencing the behavior of cells. The steroid receptor-steroid hormone complex regulates the transcription of specific genes.	Corticosteroid Receptors,Receptors, Corticosteroid,Steroid Receptors,Corticosteroid Receptor,Receptors, Steroids,Steroid Receptor,Receptor, Corticosteroid,Receptor, Steroid,Steroids Receptors
D011988	Receptors, Thyroid Hormone	Specific high affinity binding proteins for THYROID HORMONES in target cells. They are usually found in the nucleus and regulate DNA transcription. These receptors are activated by hormones that leads to transcription, cell differentiation, and growth suppression. Thyroid hormone receptors are encoded by two genes (GENES, ERBA): erbA-alpha and erbA-beta for alpha and beta thyroid hormone receptors, respectively.	Diiodotyrosine Receptors,Receptors, Diiodotyrosine,Receptors, Thyroxine,Receptors, Triiodothyronine,T3 Receptors,T4 Receptors,Thyroid Hormone Receptors,Thyroxine Receptors,Triiodothyronine Receptors,DIT Receptors,Diiodotyrosine Receptor,MIT Receptors,Monoiodotyrosine Receptors,Receptors, DIT,Receptors, MIT,Receptors, Monoiodotyrosine,Receptors, T3,Receptors, T4,T3 Receptor,T4 Receptor,Thyroid Hormone Receptor,Thyroxine Receptor
D003001	Cloning, Molecular	The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.	Molecular Cloning
D006728	Hormones	Chemical substances having a specific regulatory effect on the activity of a certain organ or organs. The term was originally applied to substances secreted by various ENDOCRINE GLANDS and transported in the bloodstream to the target organs. It is sometimes extended to include those substances that are not produced by the endocrine glands but that have similar effects.	Hormone,Hormone Receptor Agonists,Agonists, Hormone Receptor,Receptor Agonists, Hormone
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D013329	Structure-Activity Relationship	The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.	Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D018076	DNA, Complementary	Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.	Complementary DNA,cDNA,cDNA Probes,Probes, cDNA