Hormone Mechanisms of Action

Question 1

properties of hormones receptors

Answer 1

1. proteins
2. high specificity and affinity
3. limited number expressed
   4 function as signal transducers

Question 2

what happens to unbound receptors after a ligand binds elsewhere

Answer 2

some receptors have diminished unliganded effects downstream

Question 3

how does equilibrium dissociation constant relate to affinity

Answer 3

low K = high affinity receptors

Question 4

Bmax

Answer 4

the number of receptors in a given tissue as determined by a saturation analysis

Question 5

Kd

Answer 5

the concentration of hormone at which half receptors are bound

Question 6

double reciprocal plot

Answer 6

a saturation analysis where everything is plotted as 1/(quantity). attractive because it gives a straight line

1/ligand vs 1/Bound receptors

y intercept = 1/Bmax
x interept= 1/Kd

Question 7

scathcard plot

Answer 7

bound receptors vs bound receptors/ligand

slope = 1/Kd
x intercept= Bmax

Question 8

what are the techniques used to study hormone receptors?

Answer 8

1 saturation analysis
2 RNA analysis (northern blot, in situ hybridization, PCR)
3. protein analysis
4. crystal analysis
5. functional analysis

Question 9

what are the different characteristics used to classify receptors?

Answer 9

ligand bound
cellular location
structural features
transduction mechanisms

Question 10

list examples of receptors that are enzymes

Answer 10

can be tyrosine kinases (insulin growth factors)

can be threonine/serine kinases
inhibin, activin

Question 11

give an example of a receptor that is associated with an enzyme

Answer 11

• JAK cytosolic tryosine kinases
  (prolactin, growth hormones, cytokines)
• receptor often has to dimerize

Question 12

give examples of hormones that use g-protein transducers

Answer 12

catecholamines, peptides, glucagon

Question 13

what are the five mechanisms of signal transducing receptors

Answer 13

• receptor enzymes
• receptor associated enzymes
• G proteins
• ion channels
• nuclear receptors

Question 14

describe the structure of nuclear receptors

Answer 14

hormone binding segment- carboxy end
DNA binding domain
dimerization domain
trans-activation domain (where this protein interacts w/others)

Question 15

what happens when hormones bind nuclear receptors?

Answer 15

the hormone binds at the center of the receptor and is integrated into the structure of the receptor, changing the shape

when the shape changes, it changes other binding site, causing alternative proteins to be bound

Question 16

what are the downstream affects of binding a hormone to a nuclear receptor

Answer 16

causes binding of a coactivator, histones get acetylated and become more open in structure, allowing transcriptional activation

the alternative can also be true

Question 17

principles of receptor function

Answer 17

1. receptors are expressed in tissue specific patterns
2. there is not a one-to-one relationship between hormones and receptors
   one hormone can interact w/ multiple receptors and vice versa
3. the same hormone binding to a different receptor may exert different effects

4 the same receptor binding to different hormones will lead to different effects

5 receptors may be activated in different ways (by binding of ligand or through cross talk of different pathways)

6 there are many receptors for which ligands have not yet been discovered- orphan

7 unliganded receptors are not necessarily inert