3 Hormone Action pt 2 Flashcards
what makes non-classical peptide hormones non-classical?
they’re not secreted directly into circulation; most likely secreted by various cells rather than a particular endocrine organ
what are examples of non-classical peptide hormones?
adipokines (like leptin)
list the types of non-classical hormones (4)
- peptide hormones
- amino acid derivatives
- lipid hormones
- metabolites
what are examples of non-classical amino acid derived hormones?
neurotransmitters: melatonin, serotonin, histamine
what makes non-classical lipid hormones non-classical?
they have membrane receptors instead of nuclear ones
what are examples of non-classical lipid hormones?
eicosanoids
what are some examples of non-classical metabolites that act as hormones?
lactate, ketone bodies
what can happen when there’s a mutation of a receptor’s gene sequences?
disorders/disease
what kind of receptors do steroid and thyroid hormones bind to?
nuclear receptors
where are the receptors for steroid and thyroid hormones located?
intracellularly in the cytoplasm or nucleus
how do the receptors of steroid and thyroid hormones work?
they act as transcription factors; must be able to read/bind to DNA and recognize certain sequences of nucleotides.
response of nuclear receptors is (fast/slow) compared to ligand binding receptors. why?
slow; transcription and translation of proteins is necessary
true or false: there are nuclear receptors capable of binding metabolites
true
what are the receptors called that can bind fatty acids?
PPARs; they have alpha, beta, and gamma isoforms.
ligands of nuclear receptors are _____ soluble
lipid
why is it easier to make synthetic ligands for NRs? implications?
all ligands for NRs are lipid soluble and small, making it easy for them to diffuse through cell membranes.
shows huge potential in medicine for treating cancers
how do NRs contribute to metabolism when bound to metabolites?
the NRs can act as metabolite sensors that lead to transcription and translation
what mechanisms are available that can regulate ligand levels?
- precursor
- synthesis
- secretion
- activation (receptor function)
- deactivation
- elimination
what happens when a NR ligand isn’t hydrophobic enough to diffuse through the nuclear membrane?
requires a carrier protein that will separate once inside
what’s an example of a NR ligand that needs the help of carrier proteins?
bile acids
what happens once the ligand binds to a NR receptor?
receptor becomes active and starts modulating transcription of target genes to mRNA to translate into proteins
true or false: every domain of different nuclear receptors are unique to their receptor
false - all nuclear receptors have domains in common
what significant domains to NRs have in common?
- DNA-binding (DBD)
- Nuclear localization signal (NLS)
- Ligand Binding domain (LBD)
what sequence do steroid receptors usually bind to?
AGAACA
what sequence do non-steroid receptors
AGGTCA
nuclear receptors function as _____
dimers (1 hormone binds to 2 receptors)
steroid NRs function as _____ dimers
homo
non-steroid NR function as _____ dimers
hetero
the short sequences of nucleotides that are recognized by NRs are called
hormone response elements
what method can be used to identify where hormone response elements are located?
chromatin immunoprecipitation (ChIP) sequencing
describe ChiP sequencing
we have our genome and our protein of interest (POI) which is our NR
1) we make chromatin (DNA + NR) by fixing with formaldehyde
2) shear chromatin with a physical technique (like sonication)
3) use antibody attached to magnetic beads that recognize POI
4) use steel to attract magnets and pull down POI
5) destroy the POI with a protease to keep DNA intact
6) stick it in a sequencer
what are co-repressors?
interact with DNA binding proteins (histones) to ultimately repress/stop/slow down transcription when they aren’t active
what is one of the main modifications done to histones that represses gene expression?
deacetylation
what are coactivators?
work with NR and are activators of transcription factors by allowing the transcription factor complex to associate
