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Act together to coordinate functions of all body
systems
Nervous system
◦ Nerve impulses/ Neurotransmitters
◦ Faster responses, briefer effects, acts on specific
target
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Endocrine system
◦ Hormone – mediator molecule released in one part of
the body but regulates activity of cells in other parts
◦ Slower responses, effects last longer, broader
influence
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2 kinds of glands
◦ Exocrine – ducted
◦ Endocrine – ductless
 Secrete products into interstitial fluid, diffuse into blood
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Endocrine glands include
◦ Pituitary, thyroid, parathyroid, adrenal and pineal
glands
◦ Hypothalamus, thymus, pancreas, ovaries, testes,
kidneys, stomach, liver, small intestine, skin, heart,
adipose tissue, and placenta not exclusively endocrine
glands
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Hormones affect only specific target tissues
with specific receptors
Receptors constantly synthesized and broken
down
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◦ Lipid-soluble – use transport proteins
 Steroid
 Thyroid
 Nitric oxide (NO)
◦ Water-soluble – circulate in “free” form
 Amine
 Peptide/ protein
 Eicosanoid
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Response depends on both hormone and target
cell
Lipid-soluble hormones bind to receptors inside
target cells
Water-soluble hormones bind to receptors on the
plasma membrane
◦ Activates second messenger system
◦ Amplification of original small signal
Responsiveness of target cell depends on
◦ Hormone’s concentration
◦ Abundance of target cell receptors
◦ Influence exerted by other hormones
 Permissive, synergistic and antagonistic effects
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Regulated by
◦ Signals from nervous
system
◦ Chemical changes in
the blood
◦ Other hormones
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Most hormonal
regulation by
negative feedback
◦ Few examples of
positive feedback
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Natural or synthetic
compounds that
alter the hormonal
and homeostatic
systems that enable
an organism to
communicate with
and respond to its
environment.
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Exposure to EDCs
can be
environmental or
developmental.
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Age at exposure
Latency from
exposure
Mixture of
chemicals
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Dose/response
Long-term latent
effects
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The endocrine disruptors have
shared properties.
There are similarities in the
receptors and enzymes
involved in the synthesis,
release, and degradation of
hormones.
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Can be transmitted to future
generations through
epigenetic modifications or
continued exposure of
offspring to the compounds.
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There is strong evidence of
adverse reproductive
outcomes:
•Infertility
•Cancers
•Malformations
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There is growing evidence for
effects on other endocrine
systems:
•Thyroid
•Neuroendocrine
•Obesity
and metabolism
•Insulin and glucose homeostasis
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Environment
Food
Consumer products
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EDCs interfere with hormone
biosynthesis, metabolism, or
action.
Such interference results in a
deviation from normal
homeostatic control or
reproduction.
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Presents evidence that EDCs
have effects on male and
female reproduction, breast
development and cancer,
prostate cancer,
neuroendocrinology, thyroid,
metabolism and obesity, and
cardiovascular endocrinology
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Based on
•results from animal models
•human clinical observations
•epidemiological studies
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Some pathways include:
•Estrogenic
•Antiandrogenic
•Thyroid
•Neurotransmitter
receptors
and systems
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•Organochlorinated
pesticides
and industrial chemicals
•Plastics and plasticizers
•Fuels
•Others present in the
environment or in
widespread use
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industrial solvents/lubricants:
Polychlorinated biphenols (PCBs)
Polybrominated biphenols (PBBs)
Dioxins
Plastics: bisphenol A (BPA)
Plasticizers: phthalates
Pesticides: methoxychlor,
chloropyrifos, DDT
Fungicides: vinclozolin
Pharmaceuticals: DES

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Natural chemicals in food and
feed:
Phytoestrogens – genistein
and coumestrol
- widely consumed and
in infant formula (soybased)
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It is the phenolic structure:
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They are thought to mimic natural steroid
hormone and enable EDCs to interact with
steroid hormone receptors as analogs or
antagonists.
Several classes of EDCs act as antiandrogens
and as thyroid hormone receptor agonists or
antagonists.
Androgenic EDCs have been identified.
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EDCs enter the food chain and can
bioaccumulate (due to low water solubility
and high lipid solubility.
Contaminated drinking water
Breathing contaminated air and contacting
contaminated soil
Occupational exposure to pesticides and
industrial chemicals
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Challenges to discerning EDC involvement in
a particular disorder
◦ Each person’s unique exposure to a variety of
known and unknown EDCs
◦ Individual differences in metabolism, body
composition, and genetic traits
◦ Human disorders usually result from long term
chronic exposure to low levels of mixtures of EDCs
◦ Latency between exposure to EDCs and occurrence
of clinical disorder makes causal connection
difficult (may be years or decades)
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EDCs act by more than one mechanism.
An EDC may have mixed steroidal properties:
it may be both estrogenic and
antiandrogenic.
An EDC may be metabolized into different
subproducts with different properties.
Balance between estrogenic and androgenic
properties of EDCs may be significant
because reproduction in both sexes involves
an interplay of androgens and estrogens.
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Many organs are targeted by sex steroids and
vulnerable to endocrine disruption.
◦ Hypothalamic-pituitary-gonadal system
◦ Breast
◦ Uterus
◦ Cervix
◦ Vagina
◦ Brain
◦ Bone, muscle and skin
In addition, reproductive dysfunction can result from
thyroid disruption
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Interference with development and function
of the female reproductive tract can
predispose women to:
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Infertility
Ectopic gestation
Poor pregnancy outcomes
Endometriosis
Uterine fibroids
Altered anatomy and functionality
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Hypothesized that the significant increase of
breast cancer in the industrialized world in
the last 50 years may be due to exposure to
hormonally active chemicals.
Similar increase in incidence of testicular
cancer, male genital tract abnormalities, and
decrease in sperm quantity/quality suggest a
link to the introduction of these chemicals
into the environment.
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Interface between Nervous and Endocrine
systems
Controls diverse functions, such as
reproduction, stress, growth, lactation,
metabolism and energy balance,
osmoregulation, other homeostatic regulators
Mediates ability of organism to respond to
environment through rapid (neuronal) and
more sustained (endocrine) responses
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Neuroendocrine cells in brain have both
neuronal and endocrine properties
As a result, EDCs can have neurobiological
and neurotoxic effects along with endocrine
effects
Several levels of organization: the brain
(hypothalamus), the pituitary gland, and a
target organ
The reproductive Hypothalamus-PituitaryGonad (HPG) connection is the best studied in
the area of endocrine disruption
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Gonadotropin-releasing hormone (GnRH)
(also called Luteinizing hormone) is produced
in the hypothalamus and drives reproduction
throughout the life cycle. It is the primary
stimulus to the pituitary and the gonads.
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GnRH release stimulates gonadotropin
release from anterior pituitary
Gonadotropin release activates
steroidogenesis and gametogenesis in the
ovary and testes
Steroid hormones produced by the gonad act
on target tissues that release estrogen,
progestin and/or androgen receptors (AR)
Many EDCs interfere with steroid hormone
actions
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But GnRH neurons do not have steroid receptors
This means that other cells in the brain that do have
steroid receptors and that regulate GnRH cells
through afferent neural inputs are targets for EDCs
Neuronal cells with steroid receptors include those
that make neurotransmitters (such as serotonin and
dopamine) and can regulate GnRH neurons
EDCs have been shown to cause neurotoxicity to
these neurons
This is evidence of convergence of effects of EDCs on
the link between neural and endocrine systems
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