TRH: Thyrotropin-releasing hormone; a tripeptide hormone that is
released by the hypothalamus and that acts on the anterior pituitary to
stimulate the release of thyroid-stimulating hormone.
Triiodothyronine: T3; a thyroid hormone derived from the amino acid
tyrosine that contains three iodine atoms per molecule.
TSH: Thyroid-stimulating hormone or thyrotropin; a glycoprotein hor-
mone released from the anterior pituitary in response to increased levels
of TRH. TSH binds to TSH receptors on the basal membrane of epithe-
lial cells of the thyroid gland to stimulate the release of the thyroid hor-
mones, T3 and T4.
The major circulating forms of thyroid hormone are thyroxine (T4),
containing four iodine atoms per molecule, and triiodothyronine (T3),
with three iodine atoms per molecule (Figure 45-1). Of these, T3 is eightfold
more active. These are synthesized in the thyroid gland after stimulation by
thyroid-stimulating hormone (TSH). TSH binds a G protein-coupled recep-
tor to activate adenylate cyclase and trigger a signaling cascade leading to
thyroid hormone biosynthesis. TSH is released from the pituitary in response
to negative feedback by circulating levels of thyroid hormone as well as regu-
lation by circulating levels of thyrotropin-releasing hormone (TRH), a tripep-
tide synthesized in the hypothalamus.
Thyroid hormones are the only major biochemical species known to
incorporate iodine. In fact, in third-world countries, iodine deficiency is
the major cause of hypothyroidism (deficiency of thyroid hormones). Iodine
deficiency is characterized by the development of a goiter, representing
enlargement of the thyroid gland. In the developed world, where iodine defi-
ciency is rare because of the use of iodized salt, autoimmune disorders are
a leading cause of thyroid disease. These are characterized by the presence
of antibodies in the blood that either stimulate or damage the thyroid gland.
The most common examples are Graves disease, characterized by antibody
overstimulation of thyroid hormone production, and Hashimoto thyroiditis,
leading to autoimmune destruction of the thyroid gland. In addition, inherited
human disorders resulting in mutations in the thyroid hormone receptor abol-
ishing hormone binding have been reported. These individuals exhibit symp-
toms of hypothyroidism as well as a high incidence of attention-deficit
disorder. This trait is genetically dominant, indicating that the mutant recep-
tors act in a dominant negative manner.
Thyroid hormone biosynthesis (Figure 45-2) involves the concentrative
uptake of iodide into thyroid cells where it is converted into iodine by thyroid
peroxidase in the colloid space of the follicular lumen. Iodine is incorporated
into tyrosine residues of thyroglobulin contained within the colloid space at
the basal surface of the thyroid follicular cell. Tyrosine residues are iodinated
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