Lecture 15: Nuclear receptors as drug targets

Question 1

What are nuclear receptors?

Summary?

Answer 1

Control of DNA transcription
Location: cytosol and nucleus
Response: hours - days
Example: Oestrogen

Question 2

How do nuclear receptors control DNA transcription?

- Describe the process of events

Answer 2

• receptors are located in the cytosol
• ligand or drug enters the cell and binds to them
• The complex binds to DNA and initiates transcription of genes

Question 3

How does the receptor get into the nucleus?

Answer 3

• Ligand must enter the cell and bind to the receptor located in the cytosol
• Ligand causes receptor to dissociate from the heat shock protein chaperone keeping it inactive
• Ligand-receptor complex dimerises to become functional
• Moves to nucleus and initiates transcription

Question 4

Oestrogen bind to an oestrogen receptor and regulates what?

Answer 4

Growth of cells = uterus
Cholesterol production = liver
density = bone
breast cancer = tumour growth

Question 5

What are hormone receptors?

Answer 5

• Nuclear receptors are hormones, including oestrogen and testosterone
• Receptors plays an importune role in cancer development especially breast and prostate cancers
• Antagonist drugs are used to treat cancer

Question 6

What are cancers?

What is their growth derived from?

Answer 6

• Cancers are groups of cells that are mutated to grow uncontrollably and avoid cell death
• Their growth is often driven by hormones; oestrogen and testosterone

Question 7

What is the androgen receptor ?

Answer 7

Is mutated in cancer - the response to the hormone cannot be turned off

Question 8

Is an agonist or antagonist drug used to treat cancers ?

Why?

Answer 8

Antagonist - a drug which bid stop a receptor and blocks the response
- used to treat cancer to stop cell growth