CHAPTER
Endocrine Metabolism IV:
Thyroid Gland
The thyroid
gland consists of two lobes connected by
an isthmus and is positioned on the ventral surface of the
trachea just below the larynx. It receives adrenergic fibers
from the cervical ganglion and cholinergic fibers from the
vagus and is profusely vascularized by the superior and
inferior thyroid arteries. Histologically, thyroid tissue is
composed of numerous follicles lined by a single layer of
epithelial cells around a lumen filled with proteinaceous
material called
colloid.
The follicle cells, called
thyrocytes,
produce the thyroid
hormones and are derived from the entodermal pharynx.
Interspersed between follicles are specialized APUD cells
derived from the neural crest, called C-cells or
parafollic-
ular
cells. These cells produce calcitonin (CT), a polypep-
tide hormone discussed in Chapter 37.
33.1 Structure-Activity of Thyroid Hormones
The generic term “thyroid hormones” refers to the
iodinated amino acid derivatives T
3
(3,3',5-triiodo-L-
thyronine) and T
4
(3,3',5,5'-tetraiodo-L-thyronine), the
only iodinated hormones produced endogenously. T
3
is
the biologically active hormone and is, for the most part,
produced from T
4
in extrathyroidal tissues. T
4
lacks sig-
nificant bioactivity and is a hormone precursor; however,
A list of expanded acronyms appears as Appendix VIII.
since thyroidal production of T
4
and its handling by the
body are the pivotal determinants of thyroid hormone ef-
fects, the term “thyroid hormone” includes T4.
The basic structure of T
3
and T
4
is that of thyronine,
a
substituted
tyrosine
[0-(4-hydroxyphenyl)tyrosine]
(Figure 33-1). Iodine residues at positions 3 and 5 of the
inner phenolic ring confer on the outer ring a preferred
orientation approximately
1 2 0
° to the plane of the inner
ring (Figure 33-2). Hormonal activity is maximal when
the following requirements are met:
1. Iodine is present at positions 3 and 5 of the inner ring
(required for receptor binding). A natural analog of
T3, called reverse T
3
(rT3, 3,3',5/-triiodo-L-thyronine),
is inactive. Substitution of iodine by bromine
or a methyl group almost completely abolishes
the activity.
2. A substituent is present at position 3', but it need not
be iodine. One of the most potent synthetic thyroid
hormones has an isopropyl group at position 3'.
3. A hydroxyl group is present at position 4'. This group
forms a hydrogen bond with the receptor protein.
4. A substituent is absent at position 5'. This permits full
expression of the activity of the hormone. A substituent
at this position would cause steric hindrance
in binding with receptor and interfere with hydrogen
bond formation. Thus, T
4
lacks significant activity
whereas T
3
has about six times the activity of T4.
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