Cellular Mechanisms of Hormone Action

Question 1

what are two key features of hormones ?

Answer 1

• produced by the body
• lead to a change in cell state

Question 2

what do hormones complement?

Answer 2

neurotransmitters = adjacent cell contact

where as hormones are broadcasters of message

Question 3

When a hormone acts on a distant cell, it is called what?

Answer 3

endocrine

Question 4

when a hormone acts on an adjacent cell, it is called what?

Answer 4

paracrine

Question 5

when a hormone acts on the same cell , it is called what?

Answer 5

autocrine

Question 6

the endocrine system refers to what?

Answer 6

refers to glands that secrete hormones

ex) the pineal gland, hypothalamus, pituitary, thyroid, skin, parathyroids etc

Question 7

is hormone concentration lower or higher than concentration of lipids/sugars?

Answer 7

concentrations of hormones are significantly lower than concentration of amino acids, sugars, or lipids

Question 8

the specificity of hormone action is driven through what?

Answer 8

driven through receptors - different cells express different receptors

Question 9

what factors influence the degree of a response?

Answer 9

1. Delivery of hormone
   
   1. rate of synthesis
   2. proximity of target cell to hormone source
   3. dissociation constants with transport proteins
   4. rate of conversion from inactive to active forms
   5. rate of clearance by liver/kidney
2. Receptor/tissue status
   
   1. density and state of occupancy of receptors

Question 10

why do some hormones bind intracellularly vs on the cell surface?

Answer 10

it all depends on whether the hormone can pass through the lipid bilayer

Question 11

what is the classification of hormones dependent on?

Answer 11

dependent on solubility (lipophilic vs. hydrophilic) and receptor location

Question 12

what is the mediator of a group 1 hormone vs. a group 2?

Answer 12

group 1= hormone receptor complex - changes gene expression= slow

group 2= uses a 2nd messenger like cAMP to alter preexisting protein structures/activity = rapid

Question 13

group 1 hormones lead to…?

Answer 13

leads to a change in cell state which drives changes in mRNA and resulting protein expression -

-

Question 14

what are the steps in group1 hormone signalling?

Answer 14

1. diffusion- hormone diffuses across membrane
2. binding - encounters specific receptors within cell
3. translocation - activated receptor translocates to the nucleus
4. HREs- once in nucleus, activated receptor binds to hormone response elements
5. change of expression - this binding drives changes in mRNA and resulting protein expression

Question 15

What are Hormone response elements?

Answer 15

regions of DNA - contain a sequence which associate with activated receptor and nuclear receptor proteins which control the production of proteins

*each hormone induces it’s own type of hormone response element*

Question 16

hormone response elements are associated with which group of hormone?

Answer 16

group 1 hormones which regulate transcription of proteins

Question 17

What are the steps in group 2 hormone signallig?

Answer 17

1. binding - encounters specific receptors on cell membrane - typically G protein coupled receptors which carry signal across membrane
2. intracellular signalling - activated receptor drives secondary signalling cascade which propagates the signal throught the cell
3. activation of PKA - cAMP targets and activates protein kinase A
4. phosphorylation - selective phosphorylation of cellular proteins - like metabolic enzymes, nuclear transcription factors

Question 18

protein kinase A is a very potent…

Answer 18

phosphorylator

Question 19

which response is more potent - group 1 or group 2?

Answer 19

group 2 b/c the cascade elicits a much larger response per hormone molecule

Question 20

what is the role of phosphodiesterase?

Answer 20

it helps ensure rapid turnover of cAMP = rapid termination once hormone removed

they are regulated/influenced by cAMP, cGMP,hormones and calcium

Question 21

is insulin a g protein coupled receptor?

Answer 21

no

Question 22

what is type two diabetes (mellitus)?

Answer 22

insulin resistance from a decrease in insulin receptor and problems with downstream signalling

Question 23

what cause of diabetes insipidus?

Answer 23

lots of urine - too dilute, lack of response to vasopressin, mutation in AVPR2 (vasopressin receptor)

Question 24

what is Grave’s Disease?

Answer 24

autoantibodies to TSH receptor leads to increase in thyroid hormone production and hyperthyroidism

Question 25

describe how ELISA can be used to quantify hormone levels

Answer 25

Question 26

what are the steps of ELISA?

Answer 26

1. coat well of plate with EPO antibody
2. mix in equal volumes “test” serum with an enzyme labled “control” (which is an EPO sample of known concentration”
3. add a substrate that flouresces on reaction with the enzyme
4. add this mix to the reaction/assay plate and wash away unbound mix
5. quantify the amount of signal emitted

*there is an inverse relationship between the amount of flourescemce and the concentration of the substrate bound*