BISPHENOL A

A POTENTIAL THREAT AS THYROID

DISRUPTOR

PRESENTED BY: MSC(Sem-IV)-Zool-229

PAPER- MZPW-404
Department of Zoology, Visva-Bharati
SILENT SPRING

In 1962, Rachel Carson published

‘Silent Spring’, an account of the
severe reproductive toxicity of
pesticides in avian species. This
launched investigations into the role
of chemicals as potential
environmental toxins. Over the past
decades, the list of chemicals with
endocrine disrupting activity has
dramatically increased.
 ENDOCRINE DISRUPTORS & THEIR EFFECTS
An endocrine disruptor is an exogenous substance or mixture that alters function(s)
of the endocrine system and consequently causes adverse health effects in an intact
organism, or its progeny, or (sub)populations. (IPCS, 2002)
 THYROID DISRUPTORS are a sub-family of endocrine disruptors which interfere
with thyroid function by affecting the hypothalamo-pituitary-thyroid axis or directly via
thyroid hormone receptors. The alteration in hormonal homeostasis may cause
developmental defects, tumors, hypo or hyper-functions of thyroid hormones.

There are mainly 2 thyroid hormones, T3 and

T4. They play crucial roles in whole body
metabolism, having their receptors in almost
all the tissues of our body.

Thyroid receptors are nuclear receptors,

encoded by two separate genes (alpha and
beta respectively). The TRα locus generates
TRα1, TRα2, TRα3, and TR-delta-α, whereas
The TRβ locus generates TRβ1, TRβ2, TRβ3,
and TR-delta-β by using different promoters
and alternative splicing of the primary
transcripts.

Guyton and Hall, (2006) The Text Book of Medical Physiology

 Bisphenol A (BPA)
It is an industrial chemical used primarily to make polycarbonate plastic and epoxy resins –having
countless applications. It is an indispensable ingredient of all plastic goods as it makes plastics clear
and tough.
• The presence of two benzene rings linked
by carbon in BPA and by oxygen atom in T3
• BPA has two hydroxyl groups whereas T3
has one hydroxyl and one alanine group.

History-
• 1891-Bisphenol A discovered by Russian
chemist Aleksandr Dianin.
•1930s- The biochemist Edward Charles Dodds
tested BPA as an artificial estrogen.
• 1950s-BPA started to be used to harden
polycarbonate plastics, and make epoxy resin.
• 1997- Adverse effects of low dose
BPA exposure in laboratory animals were first
proposed.
 THYROID SIGNALING BY THYROID RECEPTORS
Unliganded TR are bound to DNA at thyroid
hormone response elements (TRE) as
homodimers or as heterodimers with
retinoid X-receptors (RXR). It can function as
transcriptional silencers in the absence of
hormone, as these receptors bind to a class
of co-repressor proteins denoted SMRT
(Silencing Mediator of Retinoic acid and
Thyroid hormone receptor)/NCoR (Nuclear
receptor Co-repressor) which can recruit
additional polypeptides like histone
deacetylases etc, to modify the chromatin
template.

Binding of hormone converts TRs and RXRs

into strong transcriptional activators, this is
accomplished by the release of the
SMRT/NCoR co-repressors and the
subsequent association of the receptors with
a new set of proteins that function as
transcriptional co-activators.
(Source- Sinha et al., 2014)
 MOLECULAR MECHANISM OF BPA INDUCED
THYROID DISRUPTION
To investigate further the effect of BPA in thyroid signaling Moriyama et al. performed an experiment
using TSA201 (transformed derivative of human embryonic kidney 293 cells) and a recombinant TR,
constructed by combining ligand binding domain of TRα1 or TRβ with DNA binding domain of Gal4 (an
yeast transcription factor), whose corresponding gene is UAS-E1BTATA-Luc.

RESULT
It was seen that BPA could suppress the activity
mediated by Gal4-TRα1 with respect to the
control, with no BPA.
In the presence of BPA, when amounts of T3
was increased to the medium, it showed that
BPA suppressed the transcriptional activity
mediated by Gal4-TRα1, compared to the
respective control cells.
MOLECULAR MECHANISM OF BPA INDUCED
THYROID DISRUPTION
 In case of negatively regulated genes
In case of negatively regulated genes presence
of T3 hormone will switch off the transcription
of target genes by association of nuclear co-
repressors with thyroid receptors whereas BPA
causes dissociation of nuclear co-repressors.

 In case of positively regulated genes

In case of positively regulated genes, presence
of T3 will switch on the transcription of target
genes by dissociation of nuclear co-repressors
from thyroid receptors whereas BPA causes
association of nuclear co-repressors .

(Source-Yoon et al., 2005)

 HOW TO AVOID BISPHENOL A?
• Plastic food containers are one of the • By avoiding canned products like
biggest sources of BPA. They may be vegetables, beans, soup, soda etc. All of
convenient options to store, transport these goods and more are often tainted
and reheat food stuffs. BPA free with BPA when canned, all because of a
stainless steel and glass options are protective plastic lining.
available instead of plastic containers
that do not leach BPA when micro
waved.

• BPA can easily leach from recycleable

• It was seen that BPA could leach in saliva objects from our household. It is very
from dental sealants used by dentists to fill important to know the danger a plastic water
in cavities. BPA free alternatives should be bottle or baby toy can bring with itself to
adopted for dental sealants. your household.
 KNOW YOUR PRODUCT BETTER
The recycling symbols on various products tell us if the bottle contains the
chemical compound BPA

These symbols mean that the bottle dose

not leach BPA in significant amounts

However, if the bottle has these symbols on

it then it may leach BPA into the food or
drink it contains.
 REFERENCES
• Boas M, Rasmussen UF, Main KM (2012) Thyroid effects of endocrine disrupting chemicals. Mol. Cell.
Endocrinol.355:240–248.

• Dodds EC, Lawson W (1936) Synthetic estrogenic agents without the phenanthrenenucleus. Nature
137:996.

• Guyton AC and Hall JE, (2006) The Text Book of Medical Physiology, Elsevier Saunders, XIth edition.

• IPCS (2002) Global assessment of the state-of-the-science of endocrine disruptors.Geneva, Switzerland,

World Health Organization, International Programme on Chemical Safety.

• Moriyama K, Tagami T, Akamizu T, Usui T, Saijo M, Kanamoto N, Hataya Y, Shimatsu A, Kuzuya H & Nakao K
(2002) Thyroid hormone action is disrupted by bisphenol A as an antagonist. J. Clin.
Endocrinol.Metab.87:5185-5190.

• Norris DO, (2007) Vertebrate Endocrinology. Elsevier Saunders. 4th edition

• State of the Science of Endocrine Disrupting Chemicals 2012 Summary for Decision-Makers Edited by Åke
Bergman, Jerrold J. Heindel, Susan Jobling, Karen A. Kidd, R. Thomas Zoeller]

•Yoon HG, Choi Y, Cole PA, Wong J (2005) Reading and function of a histone code involved in targeting co-
repressor complexes for repression. Mol Cell Biol. 25:324–335.

• Zoeller RT (2005) Environmental chemicals as thyroid hormone analogues: newstudies indicate that thyroid
hormone receptors are targets of industrial chemicals. Mol. Cell. Endocrinol.242:10–15.