Adjusting Cellular Sensitivity to Hormone
  1. Number of Receptors


    2. Spare Receptors - Multiple Hypotheses
     

    1. Cell has 2 pools, 1 "true" or active, 1 "spare" or inactive
    2. "Spare" R only reflect those not coupled to the response being monitored
    3. Spare R [R] [H] + [R] [HR], favors [HR] and responses to HR, allows regulation without altering Ka

  2. Location of Receptors
      3.  
    Expression on part of the cell surface regulates exposure to hormone,
    may allow directional or polar responses to hormone
     
  3. Biochemical Status of Receptors
      4.  
    1. Receptor aggregation alters surface location and may trigger cellular internalization of HR with proteolysis of H and/or R (receptor - mediated endocytosis; associated with at least temporary R inactivation and inaccessibility to H)
    2. Receptor aggregation may trigger tyrosine kinase activities that alter receptor association with hormone (Ka), other receptors or with transducers
    3. Transducer/Effector molecules may phosphorylate receptors and alter receptor associations as in 3b.
  4. Number of Transducers
      5.  
    Interactions with multiple transducer systems may deplete available molecules.
     
  5. Location of Transducers
      6.  
    Intracellular localization of transducers in membranes, near receptors make them more available than if they must diffuse along cytoskeletal elements in the cytoplasm; recruitment to one end of the cell by a highly localized receptor may make them unavailable for coupling to receptors at the other end of the cell.
     
  6. Biochemical Status of Transducers
      7.  
    1. Allosteric interactions mediated by binding to GTP/GDP, ATP, IP3,DAG, or other small molecules may activate or inactivate transducer elements.
    2. Phosphorylation, or other covalent biochemical modifications may activate or inactivate transducer elements.

  7. Number of Effectors
      8.  
    As for transducers.
     
  8. Location of Effectors
      9.  
    Proximity to receptor/transducer elements helps speed modulations of activity.
     
  9. Biochemical Status of Effectors
      10.  
    As for transducers, except that availability of suitable substrates may also alter activity levels and these may be affected by activities of transducers.