Endocrine Toxicology Flashcards
final exam (32 cards)
how are horrmes secreted usually? why?
pulsatile since there is a negative feedback mechanism
what is the steroid pyramid? explain it.
- cholesterol at the bottom (highest concentration): precursor to all steroids
- then metabolized into progestins (lower concentration)
- then metabolized into androgens (lower concentration)
- androgens are estrogen precursors (present in very low concentration): explains why estrogen receptors are very sensitive to anything that looks like an estrogen
WHO definition of an endocrine disruptor
an exogenous substance or mixture that alters function(s) of the endocrine system and consequently causes adverse health effects in an intact organism, or its progeny, or (sub)populations
effect of DDT on eggshells
thickness of shell directly related to DDT concentration (the higher the concentration, the thinner the eggshell)
examples of endocrine disruptors
- PAHs
- Bisphenol A
- cleaning products
- plasticizers
- flame retardants
- metals, plastics
- drugs
- herb-, pest-, fung-icides
Actions of Endocrine Disruptors
- mimic natural hormones
- block the effect of a hormone
- stimulate or inhibit system
- cause under- or over-production of hormones
Health effects reported for some EDCs
- obesity
- female fertility (oocyte)
- embryo development – affecting the future life of the child
- thyroid – affects many systems/functions
- male fertility (sperm)
- brain function (e.g. BPA in baby products such as bottle)
why do endocrine disruptors have the potential for long-lasting consequences?
affect gametes (sperm and oocytes) such that they are not functional or altered in a way (leading to transgenerational impact)
what is the The Developmental Origins of Health and Disease (DOHAD) based on?
on evidence that the roots of many diseases and dysfunctions occur very early in life, especially the embryo, fetus, infant, and child.
effect of under or over nutrition of pregnant women
influence on the fetus’s propensity to develop metabolic disorders including obesity, cancer and diabetes later in life
which systems and cells are more vulnerable to endocrine disruptors?
- developing germ cells (even at low doses)
- nervous system
which environmental influences in early life can affect the health and disease of the infant later in life?
- cigarette smoke,
- air pollution,
- environmental chemicals
Epigenetic Mechanisms of Endocrine Disruptors
they will:
- cause primordial germ-cell re-methylation
- altered germline DNA methylation, which leads to:
1. altered testis transcriptome, leading to spermatogenic defects
2. alter non-coding RNAs, which may lead to other diseases
potential sites for endocrine disruption
- brain: releasing factors
- pituitary: LH, FSH, GH
- liver: enzymes
- gonads: Estrogen, androgens
- blood: binding proteins
effect of POCBs on alligators, bald eagles, and cormorants
- lower levels of DHT and testosterone (meaning that chemicals are release that later Leydig function)
- leads to beak, skeletal, reproductive abnormalities
what happened to the minnows in the St. Lawrence River?
- Increased Intersex in Fish
- decreases numbers close to Iles de la Paix
how does the bioactive concentration (aka the affinity) of BPA to GPFR, ERRy, ERa, and ERb compare)
GPER < ERRy = ERa < ERb
effect of BPA
prevent translocation of ERa/B
mechanism of BPA
is nonmonotonic dose-response relationship:
- low dose: binds ERb only, leading to decrease Ca2+ in the cell from decrease mRNA production of receptor
- high dose: binds both ERa and ERb, leading to both decreased receptor and increase activation via PI3K pathway (overall increase Ca2+ entry)
health effects of OPEs
- neurotoxicity
- thyroid dysfunction
- developmental issues
- others: liver, adipose, pancreas, bone, reproductive
which subgroup of OPEs is more lipophilic, why?
triaryl (vs nontriaryl) since have more rings
what is IVIVE
- in vitro in vivo extrapolation
- make calculation to see what in vitro exposure would be in humans
effects of TMPP on cell phenotypes
- decreases cell count
- decreases lysosomes
- increases lipid droplets
- increases ROS (oxidative stress)
what are phthalates?
plasticizers
