Nuclear Hormone Receptor Signalling Pathways

Question 1

What are the main classes of receptors?

Answer 1

Ligand-gated ion channels
G-protein coupled receptors
Enzyme-linked receptors
Nuclear receptors

Question 2

Where can receptors be found?

Answer 2

Cell surface

Intracellular

Question 3

What roles does hormones play in signal transduction?

Answer 3

1st messenger

Question 4

How are hormones classified?

Answer 4

Steroids or nonsteroidal

Bases on structure + mechanism of action

Question 5

Describe steroid hormones

Answer 5

Lipid soluble = pass through membrane
Derived from cholesterol
Slower acting that nonsteroidal

Question 6

What is the process of steroid hormones?

Answer 6

Enter target cell
Bind to intracellular receptor
Activate genes
= proteins

Question 7

Describe nonsteroidal hormones

Answer 7

H2O soluble
Derived from amino acids
Faster than steroid hormones

Question 8

What is the process for nonsteroidal hormones?

Answer 8

Bind to cell surface receptor
Activates signal transduction pathway
Produce 2nd messenger

Question 9

What mechanism does nonsteroidal follow?

Answer 9

Intermediate
Activate existing enzymes
= small amount of hormone produce significant change

Question 10

What are examples of steroid hormones?

Answer 10

Androgens, oestrogens + progesterone
Corticosteroids
Mineralocorticoids
Glucocorticoids

Question 11

Where are androgens, oestrogens + progesterone found?

Answer 11

Cytoplasm

Question 12

What are androgens, oestrogens + progesterone produced by?

Answer 12

Gonads

Question 13

What are corticosteroids, mineralocorticoids, glucocorticoids produced by?

Answer 13

Adrenal gland

Question 14

What does glucocorticoids do?

Answer 14

Stimulate glucose production

Question 15

What does mineralocorticoids do?

Answer 15

Act on kidney to regulate salt + H2O balance

Question 16

Where are mineralocorticoids + glucocorticoids found?

Answer 16

Cytoplasm

Question 17

What is thyroid hormone produce by?

Answer 17

Thyroid gland

Question 18

Where is thyroid hormone found?

Answer 18

Bound to DNA in nucleus

Question 19

What does thyroid hormone do?

Answer 19

Development + regulation of metabolism

Question 20

What does vitamin D3 do?

Answer 20

Regulate Ca2+ metabolism = bone growth

Question 21

What does retinoic acid do?

Answer 21

Vertebrate development

Question 22

Where is retinoic acid found?

Answer 22

Bound to DNA in nucleus

Question 23

What is retinoic acid synthesised from?

Answer 23

Vitamin A

Question 24

What do receptors for steroid hormones form?

Answer 24

Homodimers

Question 25

What are homodimers?

Answer 25

Two identical molecules that come together

Question 26

What do other nuclear receptors form?

Answer 26

Heterodimers

Question 27

What are heterodimers?

Answer 27

Two different molecules

Question 28

Describe structure of nuclear receptors

Answer 28

``` Transactivation domain (A/B + E) DNA-binding/dimerization domain (C) Nuclear localisation domain (D) ```

Question 29

What is transactivation domain (A/B + E)?

Answer 29

Allows change in response to ligand | = change in DNA, initiating transcription

Question 30

What is DNA-binding/dimerization domain (C)?

Answer 30

Allows dimerization of receptors + binding to DNA

Question 31

What is nuclear localisation domain (D)?

Answer 31

Allows receptors to enter nucleus | OR maintain nuclear localisation

Question 32

Describe mechanism for cytoplasmic receptor activation

Answer 32

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

Question 33

What is the alternative to gene transcribed in mechanism for cytoplasmic receptor activation?

Answer 33

Gene expression inhibited Latent period = production of mRNA + protein

Question 34

Describe transcriptional activation by glucocorticoid hormone

Answer 34

Hormone binds to hormone receptor Repressor dislodged Complex receptor free to go into nucleus Binds to glucocorticoid response element = transcription

Question 35

Describe transcriptional activation by thyroid hormone

Answer 35

Thyroid diffuses into cytoplasm Bind to nuclear receptor OR bind to receptor already bound to DNA Transcription

Question 36

What is an example of steroid signalling?

Answer 36

Aldosterone

Question 37

Describe steroid signalling - aldosterone

Answer 37

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

Question 38

What does aldosterone do?

Answer 38

``` Induces expression of protein kinase (serum) SGK1 phosphorylates Nedd4-2 Prevents protein binding to ENaC = ENaC remains in membrane = increased Na+ retention ```