Page 301 - Color_Atlas_of_Physiology_5th_Ed._-_A._Despopoulos_2003

!
Hypothyroidism occurs when TSH-driven thy- proteins of certain genes in the nuclei and in-
roid enlargement is no longer able to compensate for fluence their transcription.
the T 3/T 4 deficiency (hypothyroid goiter). This type of The actions of T 3/T 4 are numerous and
goiter can also occur due to a congenital disturbance mainly involve the intermediate metabolism.
of T 3/T 4 synthesis (see below) or thyroid inflamma- The thyroid hormones increase the number of
tion. Hyperthyroidism occurs when a thyroid tumor
+
+
(hot node) or diffuse struma (e.g., in Grave’s disease) mitochondria and its cristae, increase Na -K -
results in the overproduction of T 3/T 4, independent ATPase activity and modulate the cholesterol
of TSH. In the latter case, an autoantibody against metabolism. This results in an increase in
the TSH receptor binds to the TSH receptor. Its ef- energy turnover and a corresponding rise in O 2
fects mimic those of TSH, i.e., it stimulates T 3/T 4 syn- consumption and heat production. T 3 also
thesis and secretion.
Hormones and Reproduction 1 : 40 in the plasma, where ! 99% of them tein thermogenin in brown fat (! p. 222). T 3
specifically stimulates heat production by in-
creasing the expression of the uncoupling pro-
T 3/T 4 transport. T 3 and T 4 occur at a ratio of
also influences the efficacy of other hormones.
(mainly T 4) are bound to plasma proteins: thy-
Insulin, glucagon, GH and epinephrine lose
roxine-binding globulin (TBG), thyroxine-bind-
their energy turnover-increasing effect in hy-
ing prealbumin (TBPA), and serum albumin.
pothyroidism, whereas the sensitivity to epi-
TBG transports two-thirds of the T 4 in the
nephrine increases (heart rate increases, etc.)
blood, while TBPA and serum albumin trans-
in hyperthyroidism. T 3 is thought to increase
port the rest. Less than 0.3% of the total T 3/T 4 in
blood occurs in an unbound (free) form, al-
lates growth and maturation, especially of the
though only the unbound molecules have an
brain and bones.
11 effect on the target cells. Certain drugs split T 3 the density of !-adrenoceptors. T 3 also stimu-
and T 4 from protein bonds, resulting in in- Cretinism occurs due to neonatal T 3/T 4 deficiencies
creased plasma concentrations of the free hor- and is marked by growth and maturation disorders
mones. (dwarfism, delayed sexual development, etc.) and
Potency of T 3/T 4. T 3 is 3–8 times more central nervous disorders (intelligence deficits,
potent than T 4 and acts more rapidly (half-life seizures, etc.). The administration of thyroid hor-
of T 3 is 1 day, that of T 4 7 days). Only ca. 20% of mones in the first six months of life can prevent or re-
all circulating T 3 originate from the thyroid; duce some of these abnormalities.
the other 80% are produced by the liver, kid- Iodine metabolism (! D). Iodine circulates in
neys, and other target cells that cleave iodide the blood as either (1) inorganic I (2–10 µg/L),
–
from T 4. The conversion of T 4 to T 3 is catalyzed (2) organic non-hormonal iodine (traces) and
by microsomal 5!-deiodase, which removes (3) protein-bound iodine (PBI) within T 3 and T 4
iodine from the 5! position on the outer ring (35–80µg iodine/L). The average daily require-
(! D). T 3 is therefore the more potent hor- ment of iodine is ca. 150µg; larger quantities
mone, while T 4 is mainly ascribed a storage are required in fever and hyperthyroidism (ca.
function in plasma. 250–500µg/day). Iodine excreted from the
body must be replaced by the diet (! D). Sea
The inactive form of T 3 called reverse T 3 (rT 3) is pro-
duced from T 4 when the iodine is split from the inner salt, seafood, and cereals grown in iodine-rich
ring with the aid of a 5- (not 5!-)deiodase. Approxi- soil are rich in iodine. Iodized salt is often used
mately equal amounts of T 3 and rT 3 are normally pro- to supplement iodine deficiencies in the diet.
duced in the periphery (ca. 25µg/day). When a per- Since iodine passes into the breast milk, nurs-
son fasts, the resulting inhibition of 5!-deiodase ing mothers have a higher daily requirement of
decreases T 3 synthesis (to save energy, see below) iodine (ca. 200 µg/day).
while rT 3 synthesis increases. Pituitary 5!-deiodase is
not inhibited, so TSH secretion (unwanted in this
case) is suppressed by the negative feedback.
T 3/T 4 receptors are hormone-sensitive tran-
scription factors located in the cell nuclei. Hor-
mone–receptor complexes bind to regulator
288
Despopoulos, Color Atlas of Physiology © 2003 Thieme
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