Notesale: Turn your study into money

Document Preview

Extracts from the notes are below, to see the PDF you'll receive please use the links above

---

ENDOCRINOLOGY  
 
Mechanisms  of  Hormone  Action  
 
Hormone:  chemical  substance  classified  as  peptide/steroid/amine;  synthesized  and  
secreted  by  endocrine  cells  commonly  found  in  endocrine  glands  (hypothalamus;  
anterior  +  posterior  lobes  of  pituitary;  thyroid;  parathyroid;  adrenal  cortex;  adrenal  
medulla;  gonads;  placenta;  pancreas;  kidney)  
Affinity:  ability  of  the  receptor  to  bind  to  ligand  
Specificity:  hormone  can  act  at  more  than  one  receptor  
 
Modes  of  cytokine  action:  
• Autocrine:  cytokine  act  on  cell  which  produces  it  
• Paracrine:  cytokine  act  on  adjacent  cells  
• Juxtacrine:  cytokine  released  from  cell  by  exocytosis  and  docks  onto  receptors  
on  adjacent  cells  
• Endocrine:  cytokine  enters  circulation  to  reach  distant  targets  
 
Second  Messenger  Action  
Major  mechanisms  of  hormone  action  and  associated  second  messengers  
• Adenylyl  cyclase  mechanism:  cAMP  
o Hormone  binds  to  a  receptor;  coupling  by  Gs/Gi  protein;  
activation/inhibition  of  adenylyl  cyclase;  increases/decreases  in  
intracellular  cAMP;  cAMP  amplifies  hormonal  signal  
o Hormone  binds  to  receptor  à  conformational  change  in  αs  subunit  
which  is  replaced  by  GTP  à  αs-­‐GTP  complex  migrates  and  binds  
to/activates  adenylyl  cyclase  which  then  converts  ATP  to  cAMP  à  
activation  of  PKA  by  cAMP  à  phosphorylation  of  intracellular  proteins  
o cAMP  degraded  to  inactive  5’AMP  by  phosphodiesterase  
• Phospholipase  C  mechanism:  IP3/Calcium  
o Hormone  binds  receptor  à  conformational  change  in  α-­‐subunità  GDP  
released  from  α-­‐subunit  and  replaced  by  GTP;  αq  subunit  detaches  from  
Gq  proteinà  αq-­‐GTP  complex  migrates,  binds  and  activates  PLCà  PLC  
frees  DAG  and  IP3  from  PIP2  à  IP3  increases  intracellular  calcium  via  
release  of  calcium  from  intracellular  ER/SR  storesà  calcium  and  DAG  
activate  PKC  à  protein  phosphorylation  
• Steroid  hormone  mechanism:  insulin  and  IGFs  (via  tyrosine  kinase  
mechanism)  
o Steroid  hormone  diffuses  across  cell  membrane  and  binds  close  to  C-­‐
terminus  of  target  receptor  protein  in  cytosol/nucleus  at  steroid  
responsive  elements  (SREs;  found  at  5’  region  of  target  genes);  hormone-­‐
receptor  complex  =  transcription  factor  regulating  rate  of  gene  
transcription;  new  mRNA  is  transcribed,  leaves  nucleus,  is  translated  to  
new  proteins  
• Guanylate  cyclase:  cGMP  
o Extracellular  domain  of  guanylyl  cyclase  receptor  domain  has  binding  
site  for  ANP;  intracellular  domain  has  guanylyl  cyclase  activity  
o ANP  binds  à  activates  guanylyl  cyclase  à  GTP  converted  to  cyclic  GMP  
à  cGMP  activates  cGMP-­‐dependent  kinase  à  protein  phosphorylation  
 



---