L33 How hormones act within the cell Flashcards
(27 cards)
where are steroid hormones derived from?
cholesterol
where are thyroid hormones derived from?
tyrosine within protein thyroglobulin
which ones of steroid/thyroid hormones are hydrophilic/phobic?
both hydrophobic
what is the general structure of steroid hormones and give examples of steroid hormones
contains aromatic rings
androgens eg testosterone derived from cholesterol
oestrogens such as oestradiol
aromatic ring is introduced by aromatase (aromatase inhibitors given to some with certain cancers, is a drug target)
how do hormones initiate mRNA transcription?
steroid hormone crosses cell membrane (hydrophobic)
binds to intracellular receptor in nucleus or in cytosol. if free hormone in cytosol the hormone receptor will move to nucleus
hormone-receptor complex acts as transcription factor
mRNA is transcribed
describe the basic model of transcription
core promoter (TATA box). transcription factors bind. RNA Pol 2 binds. transcription begins
what are nuclear receptors?
a class of proteins found within cells that are responsible for sensing steroid and thyroid hormones and certain other molecules
how does a nuclear receptor act and what properties do they have?
The nuclear receptors primarily regulate the initiation of transcription by directly binding to specific DNA sequences in the regulatory region of target genes called hormone response elements
At the amino terminus, they have a transcription regulation domain that interacts with other proteins that regulate transcription
they have a DNA binding domain with ‘zinc fingers’ that bind to the DNA helix
have a hormone binding domain at the carboxyl terminus which makes them specific.
also have a dimerisation domain allowing 2 nuclear receptors to work together in pairs
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 vitellogenin?
A protein that is made in the liver of egg-laying insects, molluscs, fish, reptiles and monotremes (egg-laying mammals).
It is transported in the blood and incorporated into egg-yolk as smaller proteins.
Vitellogenin has some regions of homology to apolipoprotein B
what is the most efficient oestrogen response element and where is it found?
GGTCACAGTGACC found upstream of the vitellogenin gene. leads to transcription of vitellogenin mRNA.
what is the full oestrogen response element and how is it a palindrome?
5′-C A G G T C A X X X T G A C C T G-3′
once transcribed, the transcribed version is read the same way as this is from the front
two ERE bind together facing in opposite directions to form a dimer
how does expression of oestrogen receptors ERa and ERb differ between healthy breast tissue and breast cancer?
Healthy breast tissue normally expresses more ERβ than ERα
Some types of breast cancer strongly express ERα.
Oestrogen promotes the rapid division of ERα- positive breast cancer cells.
how can ER+ breast cancers be detected and treated?
by staining sections of tumour biopsies with antibodies against the oestrogen receptor. (ERα positive cells are stained brown).
The growth and spread of these cancers can be inhibited by administering anti-oestrogen drugs such as tamoxifen.
how does tamoxifen act in the body?
it is a pro-drug. it gets converted into active form within body (4-hydroxy tamoxifen)
it binds to oestrogen binding site on oestrogen receptor which doesnt allow the receptor to acquire changed shape or bind to coactivators. therefore inhibits oestrogen binding and does not allow transcription to take place
how was the exact shape of the oestrogen/ tamoxifen/ receptor identified?
by x-ray crystallography
Where are T3 and T4 synthesised?
T4 (4 iodine groups) synthesised in the thyroid gland
the more active form, T3 (tri-iodothyronine) is produced in peripheral tissues through deiodination of T4 (removal of an Iodine group)
explain how thyroid hormones are synthesised by iodinating tyrosine molecules on thyroglobulin
thyroglobulin contains 2 tyrosine molecules
thyroid peroxidase adds 2 iodine groups to each tyrosine
thyroid peroxidase removes one tyrosine-iodine molecules and attaches it to the other, making thyroxine
the thyroxine is cleaved off the thyroglobulin to make T4
how many genes are there for thyroid hormone receptors?
2 separate genes for thryoid hormone receptors
therefore 2 separate receptors which have slightly different actions
eg TRE (thyroid hormone response element) is in front of various genes of energy metabolism and heart function that are switched on by thyroid hormones.
how do thyroid hormones play a key role in development in some species?
pituitary releases TSH to thyroid which releases T3 and T4 which helps in growth of tadpole to immature to frog or aquatic phase salamander to amphibious adult salamander
what is a similarity between thyroid hormone and steroid hormone?
both bind to nuclear receptors that promote transcription
how do thyroid hormones transcription switched off in the nucleus?
in nucleus, thyroi hormone receptors (TR) are bound to thyroid hormone response elements (TRE) in DNA
in absence of hromone, the receptors bind to repressor molecules that switch off transcription
how do thyroid hormones stimulate transcription?
co-repressor leaves the hormone receptor
coactivator binds to receptor and transcription starts
T3 binding releases proteins that repress transcription and causes binding of proteins that activate transcription
thyroid hormone receptors can pair with each other or pair with other nuclear receptors (maybe another TR (homodimer) but often different (heterodimer))
what is the life cycle of a retrovirus?
RNA in retrovirus
retrovirus attaches and enters cell
reverse transcription of RNA in retrovirus into DNA
integration of the DNA into host DNA
new virus produced, maybe death of cell
Sometimes, the virus can incorporate a region of host DNA into its sequence.
This may produce infectious RNA viruses that carry and express a host gene into the next cell that they infect.
