Clinical Biochemistry of Domestic Animals (Sixth Edition) - UMK ...

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Chapter | 20 Thyroid Function
A direct effect of thyroid hormones on cell membrane
transport has also been suggested from studies on 2-deoxyglucose
uptake ( Segal et al. , 1977 ). Pliam and Goldfine
(1977) proposed that T 3 binds to receptors on the cell membrane
and is transported by carriers into the cell.
A combination of the aforementioned mechanisms is
the most likely explanation of the mechanism of action of
thyroid hormone. A viable model patterned after the generalized
steroid hormone model is one in which (1) T 3 is
bound to a receptor site on the plasma membrane, (2) T 3 is
transported across the membrane into the cell by the carrier
protein, (3) T 3 in the cell is again bound to a carrier
protein, (4) T 3 rapidly exchanges between receptor sites on
the mitochondrion or nucleus, and (5) T 3 interacts in metabolic
processes and protein synthesis.
VIII . CATABOLISM AND EXCRETION OF
THYROID HORMONES
The thyroid hormones undergo deiodination, conjugation,
or oxidative reactions. The deiodination reaction occurs
widely in peripheral tissues and is catalyzed by deiodinases
specific for each iodine position, and the released iodine is
returned to the iodine pool. The details of the specific reactions,
however, are not yet known. The deiodinase that catalyzes
the deiodination of T 4 to T 3 in target cells is actually
participating in an activation reaction. Deiodination at the
3 position of T 4 gives rT 3 , the inactive form on the degradation
pathway. Within a cell, therefore, some of the T 4
is converted to its active form, and some is converted to
its inactive form for degradation. Some of the thyroid hormones
are conjugated in the liver and excreted in the bile
either as glucuronides or as sulfates. Also, the thyroid hormones,
being amino acids, are deaminated and decarboxylated
in the liver to form corresponding tetraiodoacetic acid
and tri-iodoacetic acid, which are excreted by the kidney.
Finally, the kidney also excretes the small amounts of free
hormones in the blood.
IX . REGULATION OF THE THYROID GLAND
A . Production and Regulation of Thyroid-
Stimulating Hormone
The thyroid gland is under the control of the thyroidstimulating
hormone (TSH), which is secreted by the anterior
pituitary gland, which in turn is mediated through the
hypothalamus and its thyrotropin-releasing hormone (TRH).
The TRH is synthesized in the anterior hypothalamus by
neurosecretory cells and then transported down axonic processes
to the anterior pituitary. There, TRH stimulates the
thyrotrophic cells to synthesize TSH. The secretion of TSH
is regulated by a classic negative feedback control system
based on the product of the target gland, thyroxine. A high
plasma concentration of free hormone, fT 4 , depresses TSH
secretion by the pituitary and, to some extent, the TRH
from the hypothalamus. The direct inhibition of the pituitary
by increased fT 4 is the faster responding of the two
tissues. At low concentrations of fT 4 , however, the hypothalamus
responds quickly by increasing its synthesis and
release of TRH, which in turn increases the synthesis and
release of pituitary TSH. In consequence, this regulatory
mechanism, which is sensitive to either high or low concentrations
of fT 4 , maintains the circulatory hormone concentrations
at the normal homeostatic level for that species.
B . Action of the Thyroid-Stimulating
Hormone on the Thyroid Gland
TSH has a number of direct effects on the thyroid gland:
the gland increases in size, the height of the follicular cell
increases, and there is a loss of colloid. The response of
the thyroid gland to TSH is modified by the intake of stable
iodine. When iodine intake is high, the action of TSH
is suppressed and the height, size, and activity of the follicular
cells decrease. When iodine intake is low, there is a
compensatory hypertrophy of the gland with an increase in
number, height, and size of the follicular cells. This is characteristic
of the iodine deficiency goiters or the nontoxic
goiters.
C . Action of the Thyroid-Stimulating
Hormone on Hormonogenesis
The effects of TSH on hormone synthesis by the thyroid follicle
are outlined in Figure 20-1 and discussed in Section V.
TSH affects every reaction in the hormone synthetic pathway
beginning with the uptake of iodine, its activation,
tyrosine iodination, coupling of the iodinated phenyls, and
hydrolysis of colloid. The two most important sites of TSH
action are the initial uptake of iodine and the final hydrolysis
of colloid to release hormones into the circulation.
D . Long-Acting Thyroid Stimulators
A second thyroid stimulatory factor has been identified
in the serum of human patients with Graves ’ disease and
appears to be closely involved in the mechanism of thyrotoxicosis
( Adams, 1958 ). It differs from TSH in that it
is cleared from the blood more slowly and produces its
thyroid-stimulating effects many hours (8 to 24) after that
of TSH. It is therefore referred to as long-acting thyroid
stimulator, or LATS. Studies of LATS have been largely in
humans where it has been closely correlated with hyperthyroidism
( Lipman et al. , 1967 ). Since the initial observations,
many other forms of delayed-acting thyroid
stimulators have been found, and all, including LATS, are
now known to be immunoglobulins of the IgG class. These