Final exam select topics-endocrinetox Flashcards
what is FeBAD
fetal basis of adult disease (changes in early life may not manifest until much later)
what are the endocrine effects of most pesticides
estrogenic or antiestrogenic or antriestrogenic
what is the deal with polyfluoroalkyl compounds (PFAs)
they have high energy CF bonds which resist degradation
what is the structure of PFAs like
many CF bonds (hydrophobic core) then hydrophobic tail of carboxylic acid or sulfonic acid
what is the half life of PFAs in humans
4-5 years!
what makes BPA bad when it should be a polymrt
some polymers are unbound so can leach out
what does BPA do to humans
alter sexual development, brain and behavioural abnormalities, obesity, sterility, miscarriage
what is another name for brominated flame retardants
polybrominated biphenyls
what are some things that polybrominated biphenyls/ brominated flame retardants do
they are endocrine disrupting and neurotoxicity so linked to T2DM and metabolic syndrome
what shape is the polybrominated biphenyls/ brominated flame retardants curve
U shape
where is polybrominated biphenyls/ brominated flame retardants found in humans
adipose and breast milk
why are these curves not like the classic dose response curve (3)
- properties of receptor
- 2 separate processes that appear to be a single one (multiple binding sites)
- desensitization and high doses
what are 3 types of receptors that EDCs often mess with
NRs for estrogen and androgens and aryl hydrocarbon receptor
what are 2 types of ERs + where do they bind
alpha and beta, to same response element but diff affinities
what are 6 EDC gene transcription mechanisms
- direct recruitment of coactivators
- direct recruitment of corepressors
- change conformation of NR so it binds coactivators another NR needs
- synergism or inhibition b/w 2 NRs bound to neighboring NREs (altering DNA conformation bc they bind so close)
- competition between 2 NR for NRE
- activation of one NR may promote degradation of another (proteosome activation)
what is the ERE
estrogen response element, BPs that receptor recognizes
what happens with alpha ER knockout
increased insulin resistance and impaired glucose tolerance
what may alpha ER control
food intake
how can ER increase maturation of adipocytes
alpha and beta ER are on preadipocytes
what does BPA do to body weight
increases adipocyte differentiation so more
what does octylphenol do
increase adipocyte resistin production
what is resistin
peptide hormone with high levels in fat people-linked to insulin resistance
how can BPA cause hyperinsulinemia
effects on ER alpha in the pancreas
what kind of curve does BPA make
inverted U shape
what does BPA seem to mimic
estradiol
which ER receptor is responsible for BPA insulin and stuff
ER alpha
what causes non classical ER effects
GPR30
what is GPR30
G protein receptor that binds estrogen (Gs)
what binds to GPR30 and what affinities
BPA and estrogen at same agonist affinities
what happens with GPR30 knockout
impaired glucose tolerance and decrease bone growth
what is the main thing that happens in epigenetic changes
changes in methylation patterns
what does methylation do to transcription
usually inhibits
what can happen with mis-methylated genes
DNA being inappropiately sliced or activated
what are the 2 points when methylation can be effected
after cell is first produced (no previous methylation) and after its normally methylated (later in life)
which generation (F) can changes in methylatin occur into to say its transgenerational
F3
what are 4 ways that obesogens can work
- direct acting on fat cells
- indirectly by affecting satiety or appetite
- favor storage of calories
- interacts with estrogen receptors, RXR-PPARgamma heteromers
what happens with PPARgamma stimulation
lipogenesis, lipid uptake, increase appetite
what is the mechanism of tributyl tin
decreases aromatase activity and increases testosterone levels AND PPARgamma and RXR receptor agonists
what can tributyl tin do to fish
turn girls into boys
what does tributyl tin do to multipotent stromal cells
makes the stem cells differentiate more into adipocytes rather than bone
what compound causes stem cells differentiate more into adipocytes rather than bone
tributyl tin
what is fabp4
marker for early adipocyte differentiation, fatty acid binding protein
what is a marker for early adipocyte differentiation
fabp4
what does tributyl tin do to fabp4
pushes stem cells into adipocyte pathway
how can we block tributyl tin from pushing stem cells into adipocyte pathway
PPARgamma antagnoinsts
