Biology Reference
In-Depth Information
effects on TH signaling obtained using amphibians make drawing parallels
with human entirely plausible (
Fini, Riu, et al., 2012
).
Besides these BFRs, over 100 environmental contaminants have been
identified as potential thyroid-disrupting chemicals (
Boas et al., 2012;
Brucker-Davis, 1998
), with certain authors suggesting that TH signaling with
its complex, multicomponent requirements for synthesis, activation, and me-
tabolism is the endocrine system that could be most prone to endocrine dis-
ruption. Compounds such as perchlorate have long been known to interfere
with TH synthesis by blocking iodine accumulation in thyreocytes. Emerging
compounds such as perfluoro compounds are prime candidates for TH dis-
ruptors (
Lopez-Espinosa, Mondal, Armstrong, Bloom, & Fletcher, 2012
).
Historically, two groups of chemicals that have received considerable atten-
tion for their endocrine-disrupting effects are the polychlorinated bisphenols
(PCBs) and the bisphenols, particularly bisphenol A (BPA). The PCBs are
well-characterized disruptors of TH signaling, whereas BPA, despite its
TH-disrupting actions, has more marked effects on signaling through the
estrogen receptor (ERs) (for review,
Welshons, Nagel, & vom Saal, 2006
)
and the estrogen-related receptors (ERRs) (
Gibert et al., 2011; Matsushima
et al., 2007
).
5.3.1 PCBs in the fetal environment and their effects on TH signaling
PCBs were developed and used early on in the past century. PCBs represent
a large group of compounds, with a theoretical number of 209 congeners.
These polymers found many uses in paints, plastics, rubbers, adhesives, inks,
insecticides, or as a flame retardant (
Lincer & Peakall, 1970
). In 1928, their
toxic effects were discovered after poisoning of workers. However, they
were widely used between 1930 and 1970 until they were banned in the
1970s. Unfortunately, PCBs and organochlorine insecticides belong to
the class of persistant organic pollutants and persist in the environment
due to their lipophilic properties. They are still present in the environment
nowadays. Many effects on endocrine systems have been reported, among
themmale reproduction disruption (
Sager, 1983
) and thyroid system disrup-
tion (
Gauger et al., 2007; Zoeller, Dowling, & Vas, 2000
).
In human, exposure to PCBs causes decreases in circulating levels of TH
(
Hallgren & Darnerud, 2002; Hallgren, Sinjari, Hakansson, & Darnerud,
2001; Salay & Garabrant, 2009
). PCBs, such as PCB180, PCB52, have re-
peatedly been found in amniotic fluid (
Bergonzi et al., 2009; Cao et al.,
2011; Lopez-Espinosa et al., 2007
). Given the crucial role of TH in brain
development, the question of the impact of
in utero
exposure to PCBs on
intellectual faculties was raised. The results are controversial: a correlation
