Thyroid Hormone, TSH, and TRH Receptors
Thyroid Hormone Receptors
Thyroid hormone receptors described in 1972
First of the receptors to be always nuclear
Cloned
PP Presentation
Forms of Receptor
b Forms
a forms
Rev-ErbAa (also called ear-1)
PP Presentation
Properties of Major TR Isoforms
Regulation of expression
Tissue Levels of TR mRNA and T3 Binding Capacity
Tissue Distribution
Ontogeny
Domain Structure
Domain Structure of the TR Molecule
A/B domain
C domain
C Domain (cont)
DNA Binding Domain
D domain
E-domain
E-domain (cont)
P-box of TR
P-Box of TR and Similar Receptors
Domain Structure of the TR Molecule
Recognition site
Recognition site (cont)
Homo- and heterodimerization
Heterodimers
Crystalography
PP Presentation
PP Presentation
Ligand Binding Domain
Transcriptional regulation
Initiation complex
PP Presentation
Co-activators -repressors (1995)
Co-repressors
Co-activators
Co-activators (cont)
Co-activators (cont)
Resistance to thyroid hormone
RTH (cont)
Possible Mechanisms for RTH
Summary of RTH Mutations
Ligand Binding Domain
TRb knock out
TRb knock out (cont)
TRa knock out
TRa knock out (cont)
TRa knock out
TRH Receptors
Binding sites (and mRNA) found not only in anterior pituitary
Distribution of TRHR binding sites and/or mRNA
Cloning of TRHR
Binding of TRH is through hydrogen bonds
TRH Receptor Structure
G protein coupled
Couples with phospholipase-C through GTP-binding protein
Desentization
Downregulation
TSH Receptors
TSH Receptors
PP Presentation
PP Presentation
Domains
Domains (cont)
Genomic structure
TSHR structure
TSHR Structure (cont)
Homologous desentization involves decreased coupling of TSH-R to Gs
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