Nucleic Acids - Hormones Flashcards
What are steroid hormones derived from?
Cholesterol (hydrophobic)
What are thyroid hormones derived from?
Tyrosine within the protein thyroglobulin (hydrophobic)
What can a cholesterol steroid hormone be converted into? How?
- androgens e.g. testosterone
- oestrogens e.g. oestradiol
- by changing the aromatic ring through aromatase enzyme
*look at slides for specific structures
How doe steroid hormones act?
- 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
Where are binding sites for nuclear hormone receptors found?
among promotor elements in the DNA
What binds to the N terminus (amino terminus) of nuclear hormone receptors?
Transcription regulation domain that interacts with other proteins that are involved in transcription
Where is the hormone binding domain in nuclear hormone receptors?
binding domain at the carboxyl terminus which makes them specific for a particular hormone
Where is the hormone binding domain in nuclear hormone receptors?
binding domain at the carboxyl terminus which makes them specific for a particular hormone
What domain is found between the carboxyl and amino terminuses in nuclear hormone receptors?
- The dimerization domain
- DNA binding domain with ‘zinc fingers’ that can bind to DNA helix
What are zinc fingers?
Loops of protein that contain a Zn2+ atom and in the case of steroid hormone receptors are coordinated with 4 cysteine residues
What is the role of vitellogenin
Delivers lipids from the liver to the egg yolk in amphibians, reptiles, birds and egg-laying mammals
In which animal is the most efficient oestrogen response element found?
- 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
What is a palindrome?
sequence that reads the sane going forwards (5’-3’) on the top strand as it reads going backwards (5’to3’) on the bottom strand
Why is a palindrome well-suited to be recognised by nuclear hormone receptors?
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
How can ER (estrogen receptor) positive breast cancers (ER+) be detected?
staining sections of tumour biopsies with antibodies against the oestrogen receptor.
Which drug can be administered to inhibit the growth and spread of ER+ breast cancers?
Anti-oestrogen drugs such as tamoxifen
How does tamoxifen inhibit oestrogen?
- 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
Where is T4 (thyroxine) synthesised and released from?
The thyroid gland
How does T3 form?
T4 loses on iodine atom in peripheral tissues to become T3, the active form of the hormone
Where are nuclear receptors for thyroid hormones found in the absence and presence of hormones?
Nuclear receptors for thyroid hormones are bound to the DNA in both cases
What happens in the absence of a bound thyroid hormone?
- The receptor binds a repressor of transcription
- Once the hormone binds, the repressor moves off and an activator of transcription takes its place
What are the roles of thyroid hormones?
- Regulation of energy metabolism and heart function
- Thyroid hormones may also help to protect against developing cancer
What is the structure of a retrovirus?
- 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.
What is the structure of a retrovirus?
- gene 1 followed by a polymerase gene followed by gene 3
- sometimes they can incorporate a region of host DNA into their sequence
What is the effect of incorporating host DNA into a retrovirus?
- normally no effect
- occasionally the host DNA may be active and generate a cancer causing retrovirus when it infects new hosts
What is the effect of incorporating host DNA into a retrovirus?
- normally no effect
- occasionally the host DNA may be active and generate a cancer causing retrovirus when it infects new hosts
What is an example of a highly mutated version of a thyroid hormone receptor found in a transforming retrovirus?
v-erbA = the virus occurs naturally and causes erythroblastosis and leukaemia in chickens
What is the mechanism behind V-erbA?
- 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
