Biology Reference
In-Depth Information
A pilot study was conducted to explore relationships between concen-
trations of PBDE low-brominated (BDE-17-154), highly brominated
PBDEs (BDE-183-209), and hydroxylated metabolites of PBDEs (OH-
PBDEs) and other measures of thyroid function in pregnant women in
California. The results indicate that PBDE levels are elevated in pregnant
women and may be correlated with elevated serum TSH (
Zota et al.,
2011
). However, this remains controversial (
Eggesbo et al., 2011
).
5.3. The case of TBBPA and its effects on TH signaling
TBBPA was first employed to replace PBDEs, the use of which caused con-
cern because of their high environmental persistency (
Eriksson, Jakobsson,
& Fredriksson, 2001
). TBBPA was supposed to be inert thanks to its
relatively short half-life in mammals (
Kuester, Solyom, Rodriguez, &
Sipes, 2007
) and its extensive metabolism in mammals including humans
(
Hakk & Letcher, 2003; Schauer, Volkel, & Dekant, 2006
). However,
TBBPA has been found repeatedly in environmental and human samples
(
Darnerud, 2008; Sjodin, Patterson, & Bergman, 2003
). In a French study,
Cariou and colleagues measured levels of TBBPA in cord serum and found
0.1
m
g TBBPA/g lipid showing first that TBBPA crosses placenta barrier
and second that TBBPA can be present in significant amounts during human
neurogenesis.
Leijs et al. (2012)
showed that both TBBPA and BDE-99
were associated with TH metabolism modifications.
Studies of thyroid disruption caused by TBBPA are mostly more recent
than for PBDEs.
In vitro
studies showed competition with TH receptors
(
Kitamura, Jinno, Ohta, Kuroki, & Fujimoto, 2002, Kitamura et al., 2005
)
when placed with T
3
.
Meerts et al. (2000)
have shown that TBBPA, like cer-
tain PBDEs, could bind transthyretin, with a 10-fold greater affinity than that
of T
4
. These data were confirmed by
Marchesini et al. (2008)
. More recently,
transient transfection studies in CV-1 cells described antagonistic effects of
TBBPA on TH signaling (
Sun et al., 2009
).
In vivo
studies on aquatic species have reported inhibitory effects of
TBBPA on
Rana pipiens
(
Iwamuro, Yamada, Kato, & Kikuyama, 2006
)
and on
X. laevis
TH signaling (
Fini et al., 2007; Jagnytsch, Opitz, Lutz, &
Kloas, 2006
;
Fig. 13.2
B). Until recently, data about the metabolic fate of
TBBPA in animal models were limited to rodents. These studies and one
study with human volunteers (
Schauer et al., 2006
) showed that TBBPA
is metabolized in both glucuronide-TBBPA and sulfate-TBBPA revealing
conjugation via phase II enzyme pathway. We recently showed that same
conjugation pathways are used in
Xenopus
, a finding that emphasizes that
