section 33.4
Biological Actions of Thyroid Hormones
777
H y d ro ly sis------ ►
(E n terop hepatic
of con ju gate
circulation)
In testin e
Bile
G lu cu ron id e/S O ,
conjugation
(liver)
T R .
. r „____
D eam ination-
(± active)
d ecarb oxylation
V
—
3'-T,
■
(inactive)
--------- 80%
5-D eiodination
I
— 3,3'-T
2
(inactive)
Liberated!
------ ►
Thyroids or urine
S tool
In testin e-
-
H ydrolysis -
of con ju gate
— B ile-
(E n tero p h ep a tic-
circulation)
- G lu cu ron id e/S O ,
conjugation
(liver)
-
20
%
D eam ination-
,d eca rb o x y la tio n
TETR A C : —
►
TRIAC
(± active)
rTRIAC
\
S tool
-------|T, contributes to the T, pool |-
-8 0 %
-5 0 %
5"-Deiodi nation
1
rT,
(inactive)
U n d erg o es rapid ]
5'deiodination
J
-
3 -T,
-------
3,3'-T
2
^
(inactive)
(inactive)
-3 0 %
5'-D eiod in ation
I
T
(active)
4
|T
3
pool
FIGURE 33-6
Metabolism of T
3
andT
4
. To, Thyronine;
3
,
3
'-T
2
, 3,3'-diiodothyronine; 3'-T, 3'-iodothyronine; TETRAC, 3,3',
5,5'-tetraiodothyroacetic acid; TRIAC, 3,3',5-triiodothyroacetic acid.
ventricular myocardium, thyroid hormone stimulates the
synthesis of myosin heavy chain
a
(MHCcr), while inhibit-
ing the synthesis of MHC/L by regulating the expression
of the respective genes. The result is that myocardium
with a higher MHCa content has higher calcium and
actin-activated ATPase activities and increased velocity
of muscle fiber shortening. Thus, the thyroid hormone-
conditioned ventricle is capable of increased contractile
performance.
Intermediary Metabolism
Thyroid hormone increases both lipolysis and lipoge-
nesis, although lipogenesis is stimulated before lipolysis,
due to early induction of malic enzyme (malate dehydroge-
nase), glucose-
6
-phosphate dehydrogenase, and fatty acid
synthase. Thyroid hormone lowers serum cholesterol lev-
els by maintaining low-density lipoprotein (LDL) recep-
tor density, by maintaining hepatic lipase activity which
catalyzes conversion of intermediate density lipoproteins
(IDL) to LDL, and probably also by maintaining lipopro-
tein lipase activity which promotes triglyceride clearance.
In liver, kidney, skeletal muscle, cardiac muscle, and adi-
pose tissue, thyroid hormone stimulates Na+,K+-ATPase
gene expression and promotes thermogenesis.
Growth and Maturation
Thyroid hormone stimulates production of IGF-I di-
rectly
(liver)
and
indirectly
(via
increased
growth
hormone, GH). In adults with hypothyroidism, basal
serum GH levels are normal, but the GH responses to
provocative stimuli, nocturnal GH secretion, and serum
IGF-I are all subnormal. In
cretinism
(infantile hypothy-
roidism), linear growth is severely retarded and the re-
sultant dwarfism is characterized by a retention of the
high upper to lower body ratio of infancy. The growth
retardation in persons with cretinism is primarily due to
delayed appearance of ossification centers in long bone,
and secondarily to a deficiency in growth factors.
