Page 299 - Color_Atlas_of_Physiology_5th_Ed._-_A._Despopoulos_2003

Thyroid Hormones thyrocolloid. The phenol ring of one DIT (or
MIT) molecule links with another DIT
The thyroid gland contains spherical follicles molecule (ether bridges). The resulting thyro-
(50–500 µm in diameter). Follicle cells synthe- globulin chain now contains tetraiodothy-
size the two iodine-containing thyroid hor- ronine residues and (less) triiodothyronine resi-
mones thyroxine (T 4, tetraiodothyronine) and dues (! C). These are the storage form of T 4 and
triiodothyronine (T 3). T 3 and T 4 are bound to T 3.
the glycoprotein thyroglobulin (! B2) and TSH also stimulates T 3 and T 4 secretion. The
stored in the colloid of the follicles (! A1, B1). iodinated thyroglobulin in thyrocolloid are re-
The synthesis and release of T 3/T 4 is controlled absorbed by the cells via endocytosis (! B3,
Hormones and Reproduction synthesize calcitonin (! p. 292). leads to the release of T 3 and T 4 (ca. 0.2 and
by the thyroliberin (= thyrotropin-releasing
C). The endosomes fuse with primary lyso-
somes to form phagolysosomes in which thy-
hormone, TRH)—thyrotropin (TSH) axis (! A,
roglobulin is hydrolyzed by proteases. This
and p. 270ff.). T 3 and T 4 influence physical
growth, maturation and metabolism. The par-
1–3 mol per mol of thyroglobulin, respec-
afollicular cells (C cells) of the thyroid gland
tively). T 3 and T 4 are then secreted into the
bloodstream (! B3). With the aid of deiodase,
Thyroglobulin, a dimeric glycoprotein (660 kDa) is
I meanwhile is split from concomitantly re-
–
synthesized in the thyroid cells. TSH stimulates the
leased MIT and DIT and becomes reavailable
transcription of the thyroglobulin gene. Thyro-
Control of T 3/T 4 secretion. TSH secretion by
loid by exocytosis (! B1 and p. 30).
the anterior pituitary is stimulated by TRH, a
11 globulin is stored in vesicles and released into the col- for synthesis.
Iodine uptake. The iodine needed for hormone
hypothalamic tripeptide (! p. 280) and in-
synthesis is taken up from the bloodstream as hibited by somatostatin (SIH) (! A and p. 270).
iodide (I ). It enters thyroid cells through sec- The effect of TRH is modified by T 4 in the
–
+
–
ondary active transport by the Na -I symport plasma. As observed with other target cells,
carrier (NIS) and is concentrated in the cell ca. the T 4 taken up by the thyrotropic cells of the
25 times as compared to the plasma (! B2). anterior pituitary is converted to T 3 by 5!-deio-
Via cAMP, TSH increases the transport capacity dase. T 3 reduces the density of TRH receptors in
–
of basolateral I uptake up to 250 times. Other the pituitary gland and inhibits TRH secretion
–
anions competitively inhibit I uptake; e.g., by the hypothalamus. The secretion of TSH and
ClO 4 , SCN and NO 2 . – consequently of T 3 and T 4 therefore decreases
–
–
Hormone synthesis. I ions are continuously (negative feedback circuit). In neonates, cold
–
–
transported from the intracellular I pool to the
–
–
apical (colloidal) side of the cell by a I /Cl anti- seems to stimulate the release of TRH via neu-
ronal pathways (thermoregulation, ! p. 224).
porter, called pendrin, which is stimulated by TSH is a heterodimer (26 kDa) consisting of an
TSH. With the aid of thyroid peroxidase (TPO) α subunit (identical to that of LH and FSH) and
and an H 2O 2 generator, they are oxidized to el- a " subunit. TSH controls all thyroid gland func-
0
ementary I 2 along the microvilli on the colloid tions, including the uptake of I , the synthesis
–
side of the cell membrane. With the help of and secretion of T 3 and T 4 (! A-C), the blood
TPO, the I reacts with about 20 of the 144 ty- flow and growth of the thyroid gland.
0
rosyl residues of thyroglobulin (! C). The
phenol ring of the tyrosyl residue is thereby Goiter (struma) is characterized by diffuse or nodu-
iodinated at the 3 and/or 5 position, yielding a lar enlargement of the thyroid gland. Diffuse goiter
protein chain containing either diiodotyrosine can occur due to an iodine deficiency, resulting in
(DIT) residues and/or monoiodotyrosine (MIT) T 3/T 4 deficits that ultimately lead to increased secre-
residues. These steps of synthesis are stimu- tion of TSH. Chronic elevation of TSH leads to the
proliferation of follicle cells, resulting in goiter
lated by TSH (via IP 3) and inhibited by development (hyperplastic goiter). This prompts an
thiouracil, thiocyanate, glutathione, and other increase in T 3/T 4 synthesis, which sometimes nor-
reducing substances. The structure of the thy- malizes the plasma concentrations of T 3/T 4 (euthyroid
286 roglobulin molecule allows the iodinated ty- goiter). This type of goiter often persists even after
rosyl residues to react with each other in the the iodide deficiency is rectified.
!
Despopoulos, Color Atlas of Physiology © 2003 Thieme
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