This document discusses how environmental pollutants can disrupt the thyroid system by interfering with thyroid hormone function and signaling pathways. Thyroid hormones are essential for brain development, metabolism, and adult physiology. Pollutants like perchlorate, PCBs, and BPA can mimic or interfere with thyroid hormones in ways that affect hormone production, transport, and activity. This disruption of the thyroid system can lead to abnormalities like neurodevelopmental issues, goiter, hypothyroidism, and potentially thyroid cancer over the long term. Specific pollutants like perchlorate and PCBs are highlighted for their thyroid disrupting characteristics and health effects.

1. Environmental pollutants as
Thyroid Disruptors
 Importance of Thyroid
Harmones
Thyroid hormones are essential for:
 Normal brain development in fetus.
 For the control of metabolism,
 For normal adult physiology.


2. What Happens in the presence
of Endocrine Disruptors?
Environmental pollutants Interfere with
the normal functioning of thyroid
hormone and produce hazaderous
effects on:
 development
 metabolism
 adult physiology
 Disturbed Thyroid Harmone signalling
pathways.


3. How Pollutants act?
Structural Similarity with THs:
Several Thyroid Disruptors have high degree
of
structural resemblance to the thyroxine (T4)
and triiodothyronine (T3) due to which they
get attach to receptor sites instead of THs.
 Interference with regulation:
 Many industrial chemicals and pollutants can
interfere with thyroid function by acting on
different points of regulation of thyroid
hormone synthesis, release, transport
through the blood, metabolism of thyroid
hormone.



4. Major Thyroid Disruptors And
Their Effects
Perchlorate
It block uptake of Iodide in thyroid cells.As a
result T3 and T4 synthesis decreased.Higher
in smoker Women.
 PCBs
 These are lipophilic in nature and accumulate
in fatty tissues.PCBs inhibit TSH receptors
and decrease production of T3 and T4. It
reduce T4 circulation in blood.
 Acetochlor(Herbicide)
 It enhance hepatic(liver) metabolism results
in increase metabolism of T3 and T4
unneccesarily



5. 



Pentachlorophenol
T4 transport to target tissues via serum
transport proteins e.g Transthyretin(TTR)
but if pentachlorophenol competitively
binds to serum transport proteins then
T4 would not be transported to target
tissue.
Bisphenol A(BPA)
At high temprature BPA leach out of
plastics into food.

6. In Human embryonic kidney cell and
hepatoblastoma cells BPA inhibit T3
binding to TR .
 Isoflavones,
 especially those found in soy protein
(e.g., genistein, coumesterol) cause
goiter in Human infants.


7. Abnormalities due to Thyroid
Disruptors
Neurodevelopmental toxicity
 Goiter and thyroid diseases are
associated with TH disruption.
 Hypothyroidism
 It results in impaired intellectual
development in childrens or
permanent cognitive deficiencies.


8. Perchlorates as Thyroid
Disruptors
Perchlorate is a known competitive
inhibitor of the sodium-iodide in
humans and can inhibit iodide
uptake, leading to the suppression of
T3 and T4.
 Effects
 It has been related to lower levels of
iodine in breast milk.As a result of
iodine deficiency neurodevelopmental
disorders occur in utero.


9. 
In an environment with perchlorate
exposure may have a significant effect on
thyroid hormone production particularly in
the environment of dietary iodine
insufficiency

10. PCBs as Thyroid Disruptors



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The concept that PCBs can exert a
neurotoxic effect on the developing brain
by causing a state of relative
hypothyroidism.
Polychlorinated biphenyls belong to the
class of organochlorine compounds
classified as persistent
organohalogenated pollutants (POPs)
Disruption Mechanisms:
(1)It reducing the ability of thyroid
hormones to bind to transport proteins in
the bloodstream

11. (2)It enhance hepatic metabolism by
up-regulating the sulfotransferases
that break down thyroid hormones in
the liver
 (3)It inhibit the production of
deiodinases that allow T4 to be
converted to T3
 (4)it act as either an agonist or
antagonist at the site of the cellular
thyroid receptor.


12. Environmental chemicals
impacting the thyroid hormone
receptor
PCBs
 BPA(4,4 isopropylidenediphenol)
 PBDEs (polybrominated
diphenylethers)


13. Thyroid Cancer

The role of TSH in activating growth and
differentiation of follicular cells have
shown that a prolonged disruption of the
pituitary-thyroid axis is linked to thyroid
neoplasia. Two mechanisms involved in
the disruption of the pituitary thyroid axis
are chemically-induced blocking of
thyroid peroxidase and inhibition of T4
deiodinases, which are known to occur
with TD exposure