Production, Regulation, and Action of
Thyroid Hormones
Histology of the Thyroid Gland
The thyroid gland contains numerous follicles,
composed of epithelial follicle cells and colloid.
Also, between follicles are clear parafollicular cells,
which produce calcitonin.
The Thyroid Gland
Thyroid Hormones
There are two biologically active thyroid
hormones:
- tetraiodothyronine (T! usually called
thyro"ine#
- triiodothyronine (T$#
%erived from modi&cation of tyrosine'
(hy is )odine )m*ortant in Thyroid
Hormone Production+
Thyroid hormones are uni,ue biological
molecules in that they incor*orate iodine in
their structure'
Thus, ade,uate iodine inta-e (diet, water# is
re,uired for normal thyroid hormone
*roduction'
.a/or sources of iodine:
- iodi0ed salt
- iodated bread
- dairy *roducts
- shell&sh
.inimum re,uirement: 12 micrograms3day
45 inta-e: 677 - 277 micrograms3day
)odine .etabolism
%ietary iodine is absorbed in the G) tract,
then ta-en u* by the thyroid gland (or
removed from the body by the -idneys#'
The trans*ort of iodide into follicular cells is
de*endent u*on a 8a
9
3)
-
cotrans*ort system'
)odide ta-en u* by the thyroid gland is
o"idi0ed by *ero"ide in the lumen of the
follicle:
peroxidas
e
I
-
I
+
Oxidied iodine can then be used in production of
thyroid hormones.
The 8e"t 5te*: Production of
Thyroglobulin
Pituitary *roduces T5H, which binds to
follicle cell rece*tors'
The follicle cells of the thyroid *roduce
thyroglobulin'
Thyroglobulin is a very large glyco*rotein'
Thyroglobulin is released into the colloid
s*ace, where it:s tyrosine residues are
iodinated by )
9
'
This results in tyrosine residues which have
one or two iodines attached
(monoiodotyrosine or diiodotyrosine#'
The Thyroid Gland ; Histology
Gland is com*osed of hollow s*heres, called colloid
follicles'
!"uamous epithelial cells, cuboidal cells #follicle cells$
%ollicle cells produce thyroglobulin ---- T&
I
'olloid fills the follicle ca(ities
Thyroid <ollicles
Thyroid <ollicles
=ne .a/or Advantage of this
5ystem
The thyroid gland is ca*able of storing
many wee-s worth of thyroid
hormone (cou*led to thyroglobulin#'
)f no iodine is available for this *eriod,
thyroid hormone secretion will be
maintained'
Regulation of Thyroid Hormone
>evels
Thyroid hormone synthesis and
secretion is regulated by two main
mechanisms:
- an ?autoregulation@ mechanism,
which reAects the available levels of
iodine
- regulation by the hy*othalamus and
anterior *ituitary
Autoregulation of Thyroid Hormone
Production
The rate of iodine u*ta-e and
incor*oration into thyroglobulin is
inAuenced by the amount of iodide
available:
- low iodide levels increase iodine
trans*ort into follicular cells
- high iodide levels decrease iodine
trans*ort into follicular cells
Thus, there is negative feedbac- regulation
of iodide trans*ort by iodide'
Action of T5H on the Thyroid
T5H acts on follicular cells of the thyroid'
- increases iodide trans*ort into follicular cells
- increases *roduction and iodination of
thyroglobulin
- increases endocytosis of colloid from lumen
into follicular cells
)a+
I
-
thyroglobulin follicle
cell
gene
I
-
endocytosis
thyroglobulin
T* T+
colloid droplet
I
-
I
+
iodination
thyroglobulin
)a+ ,+
AT-
.echanism of Action of T5H
T5H binds to a *lasma membrane-bound,
G *rotein-cou*led rece*tor on thyroid
follicle cells'
5*eci&cally, it activates a Gs-cou*led
rece*tor, resulting in increased cA.P
*roduction and PBA activation'
T!&
.sa
Adenylyl
'yclase
AT- cyclic A/-
-rotein 0inase
A
Follicle cell
Regulation of T5H Release from
the Anterior Pituitary
T5H release is inAuenced by hy*othalamic
TRH, and by thyroid hormones themselves'
Thyroid hormones e"ert negative feedbac-
on T5H release at the level of the anterior
*ituitary'
- inhibition of T5H synthesis
- decrease in *ituitary rece*tors for TRH hypothalamus
T1&
T1& receptor
T!& synthesis
pituitary T*2T+
+
-
-
)nAuence of TRH on T5H Release
Thyrotro*in-releasing hormone (TRH# is a
hy*othalamic releasing factor which travels
through the *ituitary *ortal system to act on
anterior *ituitary thyrotro*h cells'
TRH acts through G *rotein-cou*led rece*tors,
activating the )P$ (Ca
69
# and %AG (PBC#
*athways to cause increased *roduction and
release of T5H'
T1& phospholipase '
. protein-coupled
receptor
I-* calcium
3A. -,'
calmodulin
Thyroid hormones also inhibit T1& synthesis.
8egative <eedbac- Actions of
Thyroid Hormones on T5H
5ynthesis and Release
hypothalamus
T1&
T1& receptor
T!& synthesis
pituitary
T*2T+
+
-
-
-
T1& synthesis
Thyroid gland
follicle cell receptors
T!& binds
=ther <actors Regulating Thyroid
Hormone >evels
%iet: a high carbohydrate diet increases T$
levels, resulting in increased metabolic
rate (diet-induced thermogenesis#'
>ow carbohydrate diets decrease T$ levels,
resulting in decreased metabolic rate'
Cold 5tress: increases T$ levels in other
animals, but not in humans'
=ther stresses: increased or decreased+
Any condition that increases body energy
re,uirements (e.g., *regnancy, *rolonged
cold# stimulates hy*othalamus TRH
T5H (Pit#
Actions of Thyroid Hormones
Thyroid hormones are essential for normal
growth of tissues, including the nervous
system'
>ac- of thyroid hormone during develo*ment
results in short stature and mental de&cits
(cretinism#'
Thyroid hormone stimulates basal metabolic
rate'
(hat are the s*eci&c actions of thyroid
hormone on body systems+
Actions of Thyroid Hormone
Re,uired for GH and *rolactin
*roduction and secretion
Re,uired for GH action
)ncreases intestinal glucose
reabsor*tion (glucose trans*orter#
)ncreases mitochondrial o"idative
*hos*horylation (ATP *roduction#
)ncreases activity of adrenal medulla
(sym*athetic! glucose *roduction#
)nduces en0yme synthesis
Result: stimulation of growth of tissues
and increased metabolic rate' )ncreased
heat *roduction (calorigenic eDect#
EDects of Thyroid Hormone on
8utrient 5ources
EDects on *rotein synthesis and
degradation:
-increased *rotein synthesis at low thyroid
hormone levels (low metabolic rate! growth#
-increased *rotein degradation at high
thyroid hormone levels (high metabolic rate!
energy#
EDects on carbohydrates:
-low doses of thyroid hormone increase
glycogen synthesis (low metabolic rate!
storage of energy#
- high doses increase glycogen brea-down
(high metabolic rate! glucose *roduction#
=ne .a/or Target Gene of T$: The
8a
9
3B
9
ATPase Pum*
Pum*s sodium and *otassium across cell
membranes to maintain resting membrane
*otential
Activity of the 8a
9
3B
9
*um* uses u* energy, in
the form of ATP
About F3$rd of all ATP in the body is used by
the 8a
9
3B
9
ATPase
T$ increases the synthesis of 8a
9
3B
9
*um*s,
mar-edly increasing ATP consum*tion'
T$ also acts on mitochondria to increase ATP
synthesis
The resulting increased metabolic rate
increases thermogenesis (heat *roduction#'
Thyroid hormones:
Bey Points
Held in storage
Gound to mitochondria, thereby
increasing ATP *roduction
Gound to rece*tors activating genes
that control energy utili0ation
E"ert a calorigenic eDect
Thyroid Hormone Actions
which )ncrease ="ygen
Consum*tion
)ncrease mitochondrial si0e, number
and -ey en0ymes
)ncrease *lasma membrane 8a-B
ATPase activity
)ncrease futile thermogenic energy
cycles
%ecrease su*ero"ide dismutase
activity
EDects of Thyroid Hormones
on the Cardiovascular
5ystem
)ncrease heart rate
)ncrease force of cardiac contractions
)ncrease stro-e volume
)ncrease Cardiac out*ut
4*-regulate catecholamine rece*tors
EDects of Thyroid Hormones
on the Res*iratory 5ystem
)ncrease resting res*iratory rate
)ncrease minute ventilation
)ncrease ventilatory res*onse to
hy*erca*nia and hy*o"ia
EDects of Thyroid Hormones
on the Renal 5ystem
)ncrease blood Aow
)ncrease glomerular <ration rate
EDects of Thyroid Hormones
on ="ygen-Carrying
Ca*acity
)ncrease RGC mass
)ncrease o"ygen dissociation from
hemoglobin
EDects of Thyroid Hormones
on )ntermediary .etabolism
)ncrease glucose absor*tion from
the G) tract
)ncrease carbohydrate, li*id and
*rotein turnover
%own-regulate insulin rece*tors
)ncrease substrate availability
EDects Thyroid Hormones in
Growth and Tissue
%evelo*ment
)ncrease growth and maturation of bone
)ncrease tooth develo*ment and eru*tion
)ncrease growth and maturation of
e*idermis,hair follicles and nails
)ncrease rate and force of s-eletal muscle
contraction
)nhibits synthesis and increases
degradation of muco*olysaccharides in
subcutaneous tissue
EDects of Thyroid Hormones
on the 8ervous 5ystem
Critical for normal C85 neuronal
develo*ment
Enhances wa-efulness and alertness
Enhances memory and learning
ca*acity
Re,uired for normal emotional tone
)ncrease s*eed and am*litude of
*eri*heral nerve reAe"es
EDects of Thyroid Hormones
on the Re*roductive 5ystem
Re,uired for normal follicular
develo*ment and ovulation in the
female
Re,uired for the normal
maintenance of *regnancy
Re,uired for normal
s*ermatogenesis in the male
