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Production, Regulation, and Action of
Thyroid Hormones
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The Thyroid Gland
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Thyroid Hormones There are two biologically active thyroid
hormones: - tetraiodothyronine(T! usually calledthyro"ine#
- triiodothyronine (T$#
%erived from modi&cation of tyrosine'
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hy is )odine )m*ortant in ThyroidHormone Production+
Thyroid hormones are uniue biologicalmolecules in that they incor*orate iodine intheir structure'
Thus, adeuate iodine intae (diet, water# is
reuired for normal thyroid hormone*roduction' .a/or sources of iodine:
- iodi0ed salt - iodated bread
- dairy *roducts- shell&sh
.inimum reuirement: 12 micrograms3day 45 intae: 677 - 277 micrograms3day
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)odine .etabolism
%ietary iodine is absorbed in the G) tract,then taen u* by the thyroid gland (orremoved from the body by the idneys#'
The trans*ort of iodide into follicular cells isde*endent u*on a 8a93)-cotrans*ort system'
)odide taen u* by the thyroid gland iso"idi0edby *ero"ide in the lumen of thefollicle:
peroxidas
eI- I+
Oxidied iodine can then be used in production of
thyroid hormones.
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The 8e"t 5te*: Production ofThyroglobulin
Pituitary *roduces T5H, which binds tofollicle cell rece*tors'
The follicle cells of the thyroid *roduce
thyroglobulin' Thyroglobulin is a very large glyco*rotein'
Thyroglobulin is released into the colloids*ace, where its tyrosine residues are
iodinated by )9' This results in tyrosine residues which have
one or two iodines attached(monoiodotyrosine or diiodotyrosine#'
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The Thyroid Gland ; HistologyGland is com*osed of hollow s*heres, called colloid
follicles'!"uamous epithelial cells, cuboidal cells #follicle cells$
%ollicle cells produce thyroglobulin ----T&I
'olloid fills the follicle ca(ities
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Thyroid
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Thyroid
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=ne .a/or Advantage of this5ystem
The thyroid gland is ca*able of storingmany wees worth of thyroid
hormone(cou*led to thyroglobulin#'
)f no iodine is available for this *eriod,thyroid hormone secretion will bemaintained'
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Regulation of Thyroid Hormone>evels
Thyroid hormone synthesis andsecretion is regulated by two main
mechanisms:- an ?autoregulation@ mechanism,which reects the available levels ofiodine
- regulation by the hy*othalamus andanterior *ituitary
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Autoregulation of Thyroid Hormone
Production
The rate of iodine u*tae andincor*oration into thyroglobulin is
inuenced by the amount of iodideavailable:
- low iodide levels increase iodinetrans*ort into follicular cells
- high iodide levels decrease iodinetrans*ort into follicular cells
Thus, there is negative feedbac regulationof iodide trans*ort by iodide'
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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-thyroglobulinfolliclecell
gene
I-
endocytosis
thyroglobulin
T* T
colloid droplet
I-
I+
iodination
thyroglobulin
)a+ +
AT
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.echanism of Action of T5H
T5H binds to a *lasma membrane-bound,G *rotein-cou*led rece*tor on thyroidfollicle cells'
5*eci&cally, it activates a Gs-cou*led
rece*tor, resulting in increased cA.P*roduction and PBAactivation'
T!&
sa
Adenylyl
'yclase
AT cyclic A/
rotein 0inase
A
Follicle cell
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Regulation of T5H Release fromthe Anterior Pituitary
T5H release is inuenced by hy*othalamicTRH, and by thyroid hormones themselves'
Thyroid hormones e"ert negative feedbacon T5H release at the level of the anterior*ituitary'
- inhibition ofT5H synthesis
- decrease in *ituitary rece*tors for TRHhypothalamus
T1&
T1& receptor
T!& synthesispituitary T*2T
+
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)nuence of TRH on T5H Release
Thyrotro*in-releasing hormone (TRH# is a
hy*othalamic releasing factor which travelsthrough the *ituitary *ortal system to act onanterior *ituitary thyrotro*h cells'
TRH acts through G *rotein-cou*led rece*tors,activating the )P$ (Ca69# and %AG (PBC#
*athways to cause increased *roduction andrelease of T5H'
T1& phospholipase '
protein-coupled
receptor
I* calcium
3A '
calmodulin
Thyroid hormones also inhibit T1& synthesis.
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8egative
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=ther evels
%iet: a high carbohydrate diet increasesT$levels, resulting in increased metabolicrate (diet-induced thermogenesis#'
>ow carbohydrate diets decreaseT$ levels,resulting in decreased metabolic rate'
Cold 5tress: increases T$ levels in otheranimals, but not in humans'
=ther stresses: increased or decreased+
Any condition that increases body energyreuirements (e.g., *regnancy, *rolongedcold# stimulates hy*othalamus TRH T5H (Pit#
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Actions of Thyroid Hormones
Thyroid hormones are essential for normalgrowth of tissues, including the nervoussystem'
>ac of thyroid hormone during develo*mentresults in short stature and mental de&cits(cretinism#'
Thyroid hormone stimulates basal metabolic
rate'
hat are the s*eci&c actions of thyroidhormone on body systems+
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Actions of Thyroid Hormone Reuired for GH and *rolactin
*roduction and secretion
Reuired for GH action
)ncreases intestinal glucosereabsor*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' )ncreasedheat *roduction (calorigenic eDect#
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EDects of Thyroid Hormone on8utrient 5ources
EDects on *rotein synthesis anddegradation:-increased *rotein synthesis at low thyroidhormone 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 breadown(high metabolic rate! glucose *roduction#
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=ne .a/or Target Gene of T$: The8a93B9ATPase Pum*
Pum*s sodium and *otassium across cellmembranes to maintain resting membrane*otential
Activity of the 8a93B9*um* uses u* energy, in
the form of ATP About F3$rd of all ATP in the body is used by
the 8a93B9ATPase
T$ increases the synthesis of 8a93B9*um*s,
maredly increasing ATP consum*tion' T$ also acts on mitochondria to increase ATP
synthesis
The resulting increased metabolic rateincreases thermogenesis (heat *roduction#'
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Thyroid hormones:Bey Points
Held in storage ound to mitochondria, thereby
increasing ATP *roduction
ound to rece*tors activating genesthat control energy utili0ation
E"ert a calorigenic eDect
yro ormone ct ons
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yro ormone ct onswhich )ncrease ="ygen
Consum*tion )ncrease mitochondrial si0e, numberand ey en0ymes
)ncrease *lasma membrane 8a-BATPase activity
)ncrease futile thermogenic energycycles
%ecrease su*ero"ide dismutaseactivity
ects o yro ormones
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ects o yro ormoneson the Cardiovascular
5ystem )ncrease heart rate )ncrease force of cardiac contractions
)ncrease stroe volume )ncrease Cardiac out*ut
4*-regulate catecholamine rece*tors
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EDects of Thyroid Hormoneson the Res*iratory 5ystem
)ncrease resting res*iratory rate
)ncrease minute ventilation
)ncrease ventilatory res*onse tohy*erca*nia and hy*o"ia
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EDects of Thyroid Hormoneson the Renal 5ystem
)ncrease blood ow
)ncrease glomerular <ration rate
ects o yro ormones
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ects o yro ormoneson ="ygen-Carrying
Ca*acity
)ncrease RC mass )ncrease o"ygen dissociation from
hemoglobin
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EDects of Thyroid Hormoneson )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
ects yro ormones n
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ects yro ormones nGrowth 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 seletal muscle
contraction
)nhibits synthesis and increasesdegradation of muco*olysaccharides insubcutaneous tissue
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EDects of Thyroid Hormoneson the 8ervous 5ystem
Critical for normal C85 neuronal
develo*ment Enhances waefulness and alertness
Enhances memory and learning
ca*acity Reuired for normal emotional tone
)ncrease s*eed and am*litude of*eri*heral nerve ree"es
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EDects of Thyroid Hormoneson the Re*roductive 5ystem
Reuired for normal follicular
develo*ment and ovulation in thefemale
Reuired for the normal
maintenance of *regnancy Reuired for normal
s*ermatogenesis in the male
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