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clear, because the thyroid is a relatively robust gland in adults. It is able to compensate for
moderate or mild disruption by a thyroid hyperplasia known as goiter. Thus, the impact
of thyroid disruption during the development of individuals is different from that in an
adult. Indeed, THs have an essential role in fetal development. Prenatal exposure to thy-
roid disruptors will have consequences that can be very damaging, particularly in the
developing brain.
The regulation of thyroid function is a finely tuned negative feedback mechanism of
circulating THs at the hypothalamic and pituitary levels, that maintain relatively stable
serum levels of THs with each individual having it set at a specific point (Feldt-Rasmussen
et al. 1980).
The mechanisms involved in thyroid homeostasis are numerous and complex, and envi-
ronmental chemicals may interfere at all levels (Figure 8.3). Thyroid function is affected
by binding proteins, peripheral metabolism, alterations in the thyroid gland, and clear-
ance (Boas et al. 2011). In a review, Brown et al. (2004) describe the thyroid cascade and the
effects of contaminants on the teleost fish thyroid.
Unlike mammals and amphibians that have an organized pair of thyroid glands,
the majority of teleost fishes have multiple thyroid follicles, individually or in clusters,
scattered among the afferent branchial arterioles in the ventral region of the pharynx.
Nevertheless, the basic structure and function of the thyroid follicle is fairly conserved
across vertebrates (Paris et al. 2008a). The thyroid follicles are formed by a basement mem-
brane surrounding epithelial cells and enclose a lumen. Iodine is obtained by follicular
cells from the blood via a Na
+
/I symport (NIS). It is then transported to the epithelial
surface where it will form thyroxin [3,5,3,5-tetraiodo-l-thyronine (T4)] by incorporating
I into thyroglobulin. The resulting protein complex is stored in the follicle. Activation of
the neuroendocrine hypothalamo-pituitary-thyroid (HPT) axis induces the production
of THs (Eales 2006; Blanton and Specker 2007; Zoeller et al. 2007). More precisely, under
hypothalamic control, the pituitary secretes TSH, which proceeds to the thyroid gland to
activate synthesis of THs.
Biliary
excretion
Liver
Hypothalamus
T4
T3
-
Deiodination
Conjugation
TRH
TH free
TH bound
T4
T4 + T3
Peripheral
tissue
Pituitary
Blood
-
T3
Deiodination
Transport proteins
(TBG/TTR/Albumin)
TSH
T4 + T3
- Developement
- Reproduction
- Growth
- ...
T4
T3
Target
tissues
yroid
NIS
l
-
Biosynthesis
Gene transcription
Protein synthesis
FIGURE 8.3
Basic elements of thyroid function. TRH, thyrotropin-releasing hormone; TSH, thyroid stimulating hormone;
TH, thyroid hormone; NIS, sodium iodide symporter; T3, triiodothyronine; T4, thyroxine; TBG, thyroxine-
binding globulin; TTR, transthyretin; (
) main thyroid disruption endpoints.
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