1. Nuclear Receptors
By: Dr. Vahid Nikoui
Email: nikoui@razi.tums.ac.ir

2.  Regulate gene expression
 Ligands pass the cell membrane by simple
diffusion
 Receptors in the cytoplasm or in the nucleus

3. Small molecule coactivators of transcription
Steroids

4. Small molecule coactivators of
transcription
Lipid-Soluble Vitamins & Thyroid Hormone
Vitamin A
Thyroid Hormone

5. Nuclear receptor ligands are structurally diverse
 Steroids
– Estrogen (ER α,β)
– Progesterone (PR)
– Androgen (AR)
 Non-steroidal lipophilic hormones
– 1, 25-(OH)2-vitamin D3 (VDR)
– All- trans-retinoic acid (RAR α,β, γ)
– 9-cis-retinoic acid (RXR α,β, γ)
– Fatty acids (PPAR α,β, γ)
– Thyroid hormone (TR α,β)
 Orphans (No ligand or ligand unknown)

6. Steroid hormone
receptors

7. Action of Steroid Hormones versus
Peptide Hormones
Peptide Hormones Steroids
Half-life in circulation short long
Speed of action fast slow
Duration of effect short long
Location of receptor membrane inside
Post-receptor regulation high low
Signal amplification high low

9. Steroid Receptor Action
Roles of Heat Shock Proteins and HREs
hsp90
hsp70
H
hsp70
H H
R
hsp56
dimerize
H H
P?
H H
Gene
Transcription HRE target gene
5’ flanking region

12. Nuclear hormone receptor: domain structure
Zinc finger
DNA binding
domain…
inserts into
major groove
of DNA

14. Role of Phosphorylation in Steroid Receptor Activation
8-bromo cyclic AMP
PKA?
+ Phosphate
hypervariable DBD HBD
transcription

15. HETERODIMERS
CONTAINING RXR

16. T3 HORMONE
VITAMIN D3
ALL-TRANS RETINOIC ACID
9-CIS RETINOIC ACID

19. Thyroid Hormone
Receptors

23. Thyroid hormone receptors

25. THANK YOU !