Exam 1 Flashcards
Endocrine disrupting chemicals
Study of ductless glands or tissues and their hormonal products
Endocrinology
Greek for ‘to arouse or excite’
Ernest Starling “..the chemical messengers which speeding from cell to cell along the blood stream, may coordinate the activities and growth of different parts of the body”
Hormone
William Bayliss, Ernest Starling demonstrated that substance released by lining of small intestine stimulated flow of pancreatic juice in dogs
Extract of small intestine injected into dogs caused response, indicating substance was blood-borne, not nervous
Crucial Experiment, 1902
In-vivo
Yolk: nutrient for ovum in all animals except placental mammals
Mixture of proteins, lipids
Vitellogenesis Induction
Binds estrogen (and other ligands) non-covalently with hydrogen bonds, hydrophobic interactions
Steroid Binding Domain
Formula for bound hormone, B?
[(Bmax)(F)]/(Kd+F)
Accidental exposure in Italy (1976)
Increased metabolic disease in women who were children in 1976
Lower sperm quality in men who were breastfed as infants just after explosion
Dose-related association between the serum and fertility problems in women
What EDC?
Dioxin
?? binds receptor specifically through numerous weak non-covalent bonds
Ligand
Binds to estrogen response element upstream of gene to be transcribed
DNA Binding Domain
1874: Invented in Germany
1939: Insecticidal properties realized
Post WWII: Widespread use in agriculture, public health, eradicated insect-borne diseases such as malaria and typhus
DDT
Contaminated with TCDD blamed for health problems among Vietnam veterans; sprayers at high risk for prostate cancer
Agent Orange
Whole, multicellular organism
in vivo
Attaches to something larger (hormones, EDCs)
Ligand
?? indicates potential to be agonist or antagonist
Displacement
?? receptors on cell surface
Hydrophilic
What major class of hormone? mostly hydrophilic; epinephrine, thyroxine
Amine
Estradiol agonist with very high affinity for receptor
Prescribed to pregnant women 1950s-1960s to reduce early labor, miscarriage
Daughters have more reproductive problems, risk of usually rare cervix, vagina cancers
Fewer indications on sons, model of potential damage from in utero exposure
DES (diethylstilbestrol)
Measure ability of living organisms, tissues, or cells to respond to estradiol agonist
Bioassays
?? binds endocrine receptor, is weakly estrogenic (~1:1000-10,000)
BPA
Very secondary sources of BPA (4)?
Plastics, dust, dental sealants, thermal paper
2 EDCs that aren’t estrogen agonists or antagonists?
Tributylin, Atrazine
Yeast expresses human ERs; human cDNA integrated into yeast genome
Yeast-Based Reporter Gene Assay
What are the 4 EDCs that are estrogenic agonists?
Octylphenols, BPA, Phthalates, DDT
in a test tube/petri dish
in vitro