Exam 1 Flashcards by Emily Himsel

Study of ductless glands or tissues and their hormonal products

Endocrinology

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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

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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

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In-vivo
Yolk: nutrient for ovum in all animals except placental mammals
Mixture of proteins, lipids

Vitellogenesis Induction

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Binds estrogen (and other ligands) non-covalently with hydrogen bonds, hydrophobic interactions

Steroid Binding Domain

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Formula for bound hormone, B?

[(Bmax)(F)]/(Kd+F)

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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

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?? binds receptor specifically through numerous weak non-covalent bonds

Ligand

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Binds to estrogen response element upstream of gene to be transcribed

DNA Binding Domain

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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

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Contaminated with TCDD blamed for health problems among Vietnam veterans; sprayers at high risk for prostate cancer

Agent Orange

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Whole, multicellular organism

in vivo

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Attaches to something larger (hormones, EDCs)

Ligand

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?? indicates potential to be agonist or antagonist

Displacement

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?? receptors on cell surface

Hydrophilic

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What major class of hormone?
mostly hydrophilic; epinephrine, thyroxine

Amine

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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)

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Measure ability of living organisms, tissues, or cells to respond to estradiol agonist

Bioassays

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?? binds endocrine receptor, is weakly estrogenic (~1:1000-10,000)

BPA

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Very secondary sources of BPA (4)?

Plastics, dust, dental sealants, thermal paper

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2 EDCs that aren’t estrogen agonists or antagonists?

Tributylin, Atrazine

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Yeast expresses human ERs; human cDNA integrated into yeast genome

Yeast-Based Reporter Gene Assay

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What are the 4 EDCs that are estrogenic agonists?

Octylphenols, BPA, Phthalates, DDT

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in a test tube/petri dish

in vitro

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In vitro Responses to E2: proliferation, progesterone receptor up-regulation Assesses proliferation in vitro by measuring DNA

MCF-7 Cell Line

Kd formula?

([H]{R})/[H*F]

Communication between cells

Cell Signaling

Signal cell, target cell connected by gap junctions; signal passed directly from one cell to another

Direct Cell Signaling

Organized by Theo Culburn; assessed EDC research in wildlife, humans; projected that EDCs had potential to impact wildlife populations, human fertility, human health

Wingspread Conference, 1991

Binds receptors, no response

Antagonist

Proposed that developmental alterations in wildlife due to chemicals that disrupted endocrine system of developing organisms. Implications that in utero exposure causes health issues not observed until later in life. Introduced term "endocrine disruptor"

Wingspread Consensus Statement

``` Which major class of hormone? Hydrophobic; cortisol, testosterone, estradiol, progesterone ```

Steroids

Hormones transported by ?? system

circulatory

Signaling cell releases chemical messenger Messenger carried in extracellular fluid Nervous systems: Neurotransmitter released into adjacent synaptic cleft

Indirect Cell Signaling

Dose-response relationship in which curve changes direction, also called 'low dose response'

Non-Monotonic Dose Response

``` Which major class of hormone? Hydrophilic; insulin, growth hormone, secretion ```

Peptides and Proteins

Profiled many facets of DDT, such as ability to accumulate in food chain

"Silent Spring" Rachel Carson, 1962

Sexually mature fish (adult) collected from ?? downriver sewage outfall, known for higher percentage of intersex fish 6 males, 3 females housed in spawning aquaria; males competed for females Males intersex status compared to reproductive success

England River, UK

Radiolabeled substrate releases 3H20 when metabolized by enzyme

Aromatase Assay

What are the 4 receptor characteristics?

Specific binding, high affinity, saturation, signal transduction

Activates RNA polymerase

Transactivation Domain

Overproduction of estrogen in men leads to enlarged breasts, low libido, low sperm count, etc... Had symptoms of estrogen excess but endogenous estrogen levels undetectable Seldom wore gloves when applying 'base cream' to corpses

Mortician's Base Cream

Battery of tests to determine if chemicals present risk to endocrine systems in humans, wildlife

Endocrine Disruptor Screening Program (EDSP)

?? usually inside cell

hydrophobic

What is the primary source of BPA?

Linings of metal food cans

Detected in 95% of samples from survey of US populations, reference/safe dose= 50 ug/kg-bw/day

BPA

Why are rodents good model for in utero effects?

Rodents at birth= human fetus in the second trimester

Progressive increase in the amount of a substance in an organisms which occurs because the rate of intake exceeds the organism's ability to remove the substance from the body

Bioaccumulation

Anti-foulant in marine paint, may be an aromatase inhibitor

Tributyltin

Binds receptors, initiates a response

Agonist

Converts androgens into estrogens Enzyme in many tissues including gonads, brain Important factor in sexual development

Aromatase

Most widely used herbicide in US Feminized amphibians Suggested to induce aromatase

Atrazine

Does BPA free mean free of EDCs?

No, when it is removed it has to be replaced with another EDC

Binds estrogen receptor (ER), liganded ERs form dimers; is transcription factor for genes induced by this

Estradiol

If Kd is high, what is the affinity?

low

?? changes shape when ligand binds

Receptor

Consumed BPA excreted largely in ??

urine

What year? EPA banned DDT; declining benefits, environmental, topological effects DDT in environment, wildlife has decreased, but is persistent Still used in Africa, India to control malaria

1972

Exogenous chemicals that can interfere with hormone actions

Endocrine Disrupting Chemicals

Cane toad feminization associated with degree of ??

agriculture

Exam 1 Flashcards

Endocrine disrupting chemicals (60 cards)