Chapter 12 and 13 (exam 3) Flashcards
Reproductive Vulnerable
- direct tox to cells of reproductive system
- rapidly proliferating cells are targeted by ionizing radiation (oxidative damage leads to apoptosis)
–affects spermatogenesis in males, germ cell production in females
- alkylating agents bind to DNA
- Benzo[a]pyrene and other PAHs caan be found in the ovaries of smokers
endocrine system
- regulatory system of chemical messengers susceptible to chemical impacts - hormones are effective at very low concentrations
- reproductive processes regulated by hypothalamic-pituitary-gonadal axis (HPG)
–CNS-hypothalamus - secretes gonadotropic releasing hormone (GnRH)
–GnRH to pituitary gland - secretes follicle stimulating hormone (FSH) and luteinizing hormone (LH)
–FSH and LH to gonads - stimulate gonadal hormone synthesis and gametogenesis
Reproductive Endocrine Regulation
-complex feedback systems = tightly regulate processes
–hormone cascade provide several sites for signal to be regulated for tighter control
–subtle modification of tightly regulated system can have significant effects
“Our Stolen Future”
- decreased sperm in industrialized nations
- reproductive deformaties in wildlife
–lake Apopka had alligators subjected to Dicofol
- effects in otters, gulls, minks
- “you’re not half the man your father was” - Colburn
- focus on steroid and thyroid hormone impacts
- Dicofol is persistant and similar in structure to DDT, feminizes males
Types of hormones
peptides-small proteins
–insulin, epinephrine
–amino acid derivatives
Thyroid - based on retinoic acid
Steroid - based on cholesterol
Estrogen - (17-B-estradiol or E2) - binds to cytosolic estrogen receptor (ER)
–E2-ER complex enters the nucleus and binds to a response element on the DNA
–regulates gene expression
–similar to induction
Estrogen REceptor
- more primitive than others, conserved and many generations
- less binding specificity than in more evolutionary developed receptors
- more prone to inappropriate binding
- sesceptible to binding by wider variety of structures
- “Promiscuous receptor”
Estrogen Agonist
many types of structures that can be estrogen agonists
-measure using relative estrogenic reponse (%)
17-B-estradiol = 100%
DDE = 0.00004%
DDE - eggshell thinning due to calcium deposition - estrogen regulated process
Bio magnification
bioconcentration - increase in concentration of a chemical in biological tissue compared to inorganic environment (not from food)
– conc of organism / conc of environ = bioconcentration factor
Bioaccumulation - bioconc plus uptake through diet
Biomagnification - bioaccumulation over multiple level of the food chain
Long Island Sound Biomag example
- water conc = 0.000003 mg/kg DDT
- minnows 0.5 mg/kg
large fish 2.0
brids of prey 25
DDT is persistant and nonpolar - sticks around long enough to cause an effect
Relative Estrogen Effects
-greatest impact where balcground is the least
–increase in E2 will be greatest compared to background
- greatest impact on juveniles - earlier onset of puberty
- male susceptibility is greater in juveniles
–both have about zero background but juveniles are not developed and more vulneable
–increase breasts, decrease testes, increase feminization and loss of masculinity
—marijuana contains phytoestrogens
—soy products
-females - earlier onset of puberty in juveniles
Yeast Estrogen Screen
- easy to work with
- yeast cells transfected with human estrogen receptor
- ER tied to LUX gene - “firefly” gene that produces luciferase
- when compound binds to ER, upregulates luciferase production
luminosity is proportional to estrogenicity (% of E2 extivity)
(-) control - absence of estrogenic compounds
(+) control - E2
Lum chem / lum E2
MCF-7
- breast cancer proliferation assay
- in vitro uses human breast cancer cells
- estrogen sensitive, cell line proliferates when E2 binds to the ER
- promoter - increase growth of cancer cells
growth proportional to estrogenicity
wastewater treatment effluent
- wastewater can contain natural or synthetic estrogens (birth control) or chemicals from household products that can be estrogenic (pharmaceuticals, personal care products)
- not completely removed during treatment, released into water
Vitellogenin (VTG) Production
- protein associated with egg yolk production, should only be present in reproductive females
- males produce VTG if exposed to estrogenic compounds
——–other endocrine endpoint ———-
– shifts in sex ratio of offspring
–amphibians and fish have gender plasticit (not exclusively determined by genetics), exposure to environmental estrogen can shift sex ratio of adult fish and can lead to male amphibians producing oocytes or mature eggs
Atrazine
- herbicide on corn
- found in rain during spring
- decrease amphibians because very high exposure dur to habitat, compare to respiratory exposure in humans
- parent exposed - offspring impacts - F2 generation impacts
epigenetics - change how genes are expressed but chromosome not changed
