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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 &ltration 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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