Nucleic Acids - Hormones

Question 1

What are steroid hormones derived from?

Answer 1

Cholesterol (hydrophobic)

Question 2

What are thyroid hormones derived from?

Answer 2

Tyrosine within the protein thyroglobulin (hydrophobic)

Question 3

What can a cholesterol steroid hormone be converted into? How?

Answer 3

• androgens e.g. testosterone
• oestrogens e.g. oestradiol
• by changing the aromatic ring through aromatase enzyme

*look at slides for specific structures

Question 4

How doe steroid hormones act?

Answer 4

• Diffuse across the plasma membrane
• bind to their receptor in cytosol or in some cases the empty receptor is in the nucleus (already bound to DNA)
• If in cytosol, the hormone-receptor complex moves to the nucleus, acts as a transcription factor

Question 5

Where are binding sites for nuclear hormone receptors found?

Answer 5

among promotor elements in the DNA

Question 6

What binds to the N terminus (amino terminus) of nuclear hormone receptors?

Answer 6

Transcription regulation domain that interacts with other proteins that are involved in transcription

Question 7

Where is the hormone binding domain in nuclear hormone receptors?

Answer 7

binding domain at the carboxyl terminus which makes them specific for a particular hormone

Question 7

Where is the hormone binding domain in nuclear hormone receptors?

Answer 7

binding domain at the carboxyl terminus which makes them specific for a particular hormone

Question 8

What domain is found between the carboxyl and amino terminuses in nuclear hormone receptors?

Answer 8

• The dimerization domain
• DNA binding domain with ‘zinc fingers’ that can bind to DNA helix

Question 9

What are zinc fingers?

Answer 9

Loops of protein that contain a Zn2+ atom and in the case of steroid hormone receptors are coordinated with 4 cysteine residues

Question 10

What is the role of vitellogenin

Answer 10

Delivers lipids from the liver to the egg yolk in amphibians, reptiles, birds and egg-laying mammals

Question 11

In which animal is the most efficient oestrogen response element found?

Answer 11

• upstream of the vitellogenin gene in the African clawed toad (Xenopus)
• The Xenopus oestrogen response element in Vitellogenin is a palindrome

*female frogs and toads lay a large number of eggs and synthesise a lot of vitellogenin

Question 12

What is a palindrome?

Answer 12

sequence that reads the sane going forwards (5’-3’) on the top strand as it reads going backwards (5’to3’) on the bottom strand

Question 13

Why is a palindrome well-suited to be recognised by nuclear hormone receptors?

Answer 13

The two nuclear hormone receptors in the dimer pair face in opposite direction so they interact with the two elements of the palindrome which run in different directions on the DNA strand

Question 14

How can ER (estrogen receptor) positive breast cancers (ER+) be detected?

Answer 14

staining sections of tumour biopsies with antibodies against the oestrogen receptor.

Question 15

Which drug can be administered to inhibit the growth and spread of ER+ breast cancers?

Answer 15

Anti-oestrogen drugs such as tamoxifen

Question 16

How does tamoxifen inhibit oestrogen?

Answer 16

• Tamoxifen molecule binds to oestrogen receptor preventing oestrogen binding
• the tamoxifen receptor cannot bind to co-activators
• Transcription of oestrogen responsive genes do not occur and the presence of tamoxifen/oestrogen receptor complexes occupying the binding sites on DNA blocks oestrogen action

Question 17

Where is T4 (thyroxine) synthesised and released from?

Answer 17

The thyroid gland

Question 18

How does T3 form?

Answer 18

T4 loses on iodine atom in peripheral tissues to become T3, the active form of the hormone

Question 19

Where are nuclear receptors for thyroid hormones found in the absence and presence of hormones?

Answer 19

Nuclear receptors for thyroid hormones are bound to the DNA in both cases

Question 20

What happens in the absence of a bound thyroid hormone?

Answer 20

• The receptor binds a repressor of transcription
• Once the hormone binds, the repressor moves off and an activator of transcription takes its place

Question 21

What are the roles of thyroid hormones?

Answer 21

• Regulation of energy metabolism and heart function
• Thyroid hormones may also help to protect against developing cancer

Question 22

What is the structure of a retrovirus?

Answer 22

• gene 1 followed by a polymerase gene followed by gene 3
• sometimes they can incorporate a region of host DNA into their sequence which can make them infectious and carry the host gene into the next cell they infect.

Question 23

What is the structure of a retrovirus?

Answer 23

• gene 1 followed by a polymerase gene followed by gene 3
• sometimes they can incorporate a region of host DNA into their sequence

Question 24

What is the effect of incorporating host DNA into a retrovirus?

Answer 24

• normally no effect
• occasionally the host DNA may be active and generate a cancer causing retrovirus when it infects new hosts

Question 24

What is the effect of incorporating host DNA into a retrovirus?

Answer 24

• normally no effect
• occasionally the host DNA may be active and generate a cancer causing retrovirus when it infects new hosts

Question 25

What is an example of a highly mutated version of a thyroid hormone receptor found in a transforming retrovirus?

Answer 25

v-erbA = the virus occurs naturally and causes erythroblastosis and leukaemia in chickens

Question 26

What is the mechanism behind V-erbA?

Answer 26

• It binds to the TRE (thyroid hormone response element) of various thyroid hormone responsive genes
• cannot activate transcription and prevents the efficient binding of normal thyroid hormone receptors
• blocks thyroid hormone action