Nuclear Hormone Receptor Signalling Pathways Flashcards
What are the main classes of receptors?
Ligand-gated ion channels
G-protein coupled receptors
Enzyme-linked receptors
Nuclear receptors
Where can receptors be found?
Cell surface
Intracellular
What roles does hormones play in signal transduction?
1st messenger
How are hormones classified?
Steroids or nonsteroidal
Bases on structure + mechanism of action
Describe steroid hormones
Lipid soluble = pass through membrane
Derived from cholesterol
Slower acting that nonsteroidal
What is the process of steroid hormones?
Enter target cell
Bind to intracellular receptor
Activate genes
= proteins
Describe nonsteroidal hormones
H2O soluble
Derived from amino acids
Faster than steroid hormones
What is the process for nonsteroidal hormones?
Bind to cell surface receptor
Activates signal transduction pathway
Produce 2nd messenger
What mechanism does nonsteroidal follow?
Intermediate
Activate existing enzymes
= small amount of hormone produce significant change
What are examples of steroid hormones?
Androgens, oestrogens + progesterone
Corticosteroids
Mineralocorticoids
Glucocorticoids
Where are androgens, oestrogens + progesterone found?
Cytoplasm
What are androgens, oestrogens + progesterone produced by?
Gonads
What are corticosteroids, mineralocorticoids, glucocorticoids produced by?
Adrenal gland
What does glucocorticoids do?
Stimulate glucose production
What does mineralocorticoids do?
Act on kidney to regulate salt + H2O balance
Where are mineralocorticoids + glucocorticoids found?
Cytoplasm
What is thyroid hormone produce by?
Thyroid gland
Where is thyroid hormone found?
Bound to DNA in nucleus
What does thyroid hormone do?
Development + regulation of metabolism
What does vitamin D3 do?
Regulate Ca2+ metabolism = bone growth
What does retinoic acid do?
Vertebrate development
Where is retinoic acid found?
Bound to DNA in nucleus
What is retinoic acid synthesised from?
Vitamin A
What do receptors for steroid hormones form?
Homodimers
What are homodimers?
Two identical molecules that come together
What do other nuclear receptors form?
Heterodimers
What are heterodimers?
Two different molecules
Describe structure of nuclear receptors
Transactivation domain (A/B + E) DNA-binding/dimerization domain (C) Nuclear localisation domain (D)
What is transactivation domain (A/B + E)?
Allows change in response to ligand
= change in DNA, initiating transcription
What is DNA-binding/dimerization domain (C)?
Allows dimerization of receptors + binding to DNA
What is nuclear localisation domain (D)?
Allows receptors to enter nucleus
OR maintain nuclear localisation
Describe mechanism for cytoplasmic receptor activation
Ligand enters cell + causes receptor activation
Binding dislodges repressor protein
Ligand-receptor complex enters nucleus
Binds to specific DNA sequence
In promotor region
Specific sequence = hormone response element
Gene transcribed + translated = protein
What is the alternative to gene transcribed in mechanism for cytoplasmic receptor activation?
Gene expression inhibited
Latent period
= production of mRNA + protein
Describe transcriptional activation by glucocorticoid hormone
Hormone binds to hormone receptor
Repressor dislodged
Complex receptor free to go into nucleus
Binds to glucocorticoid response element = transcription
Describe transcriptional activation by thyroid hormone
Thyroid diffuses into cytoplasm
Bind to nuclear receptor
OR bind to receptor already bound to DNA
Transcription
What is an example of steroid signalling?
Aldosterone
Describe steroid signalling - aldosterone
Stimulate renal Na+ stimulation
Na+ reabsorption depends upon epithelial Na+ channel
In cortical collecting duct
CDC cells express protein Nedd4-2
It binds to ENaC = channels internalised
Limits rate of Na recovery = Na+ lost in urine
What does aldosterone do?
Induces expression of protein kinase (serum) SGK1 phosphorylates Nedd4-2 Prevents protein binding to ENaC = ENaC remains in membrane = increased Na+ retention
