Endocrine

biohemistry
 The Endocrine System
Hormone
The action
Endocrine System
Hormone action

The Endocrine System 0

• The nervousThe Endocrine

and endocrine System
systems act as a coordinated
interlocking super system, the neuroendocrine system.
•• The
The endocrine
nervous and system controls
endocrine body activities
systems by releasing
act as a coordinated
mediator
interlocking molecules called the
super system, hormones.
neuroendocrine system.
– hormones released into the bloodstream travel throughout the body
•– Theresults
endocrine
may takesystem
hours, butcontrols
last longerbody activities by releasing
• mediator
The nervous molecules
systemcalled
controlshormones.
body actions through nerve
– hormones released into the bloodstream travel throughout the body
–
impulses.
results may take hours, but last longer
– certain parts release hormones into blood
•– The nervous
rest system controls
releases neurotransmitters body
excite actions
or inhibit nerve,through nerve
muscle & gland cells
– impulses.
results in milliseconds, brief duration of effects
– certain parts release hormones into blood
– rest releases neurotransmitters excite or inhibit nerve, muscle & gland cells
– results in milliseconds, brief duration of effects

The nervous system causes muscles to contract or glands to

secrete. The endocrine system affects virtually all body tissues
 0

The nervous system causes muscles to contract or glands to

secrete. The endocrine system affects virtually all body tissues
by
Thealtering
nervousmetabolism, regulating
system causes musclesgrowth and development,
to contract or glands toand
influencing
secrete. Thereproductive processes.
endocrine system affects virtually all body tissues
by altering metabolism, regulating growth and development, and
influencing
Parts of thereproductive processes.
nervous system stimulate or inhibit the release of
hormones.
Parts of themay
Hormones nervous
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system
promote stimulate
or inhibit or inhibit the
the generation of release
nerve of
hormones.
impulses.
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Hormones may promote or inhibit the generation of nerve
impulses.

General Functions of Hormones

General Functions
• of
HelpHormones
regulate:
– extracellular fluid
– metabolism
•– Helpbiological
regulate:clock
– extracellular
contraction offluid
cardiac &
– metabolism
smooth muscle
– biological clock
glandular secretion
– contraction
some immune of cardiac &
functions
• smooth
Growth muscle
& development
•– Reproduction secretion
glandular
– some immune functions
• Growth & development
• Hormones have powerful effects
• Reproduction
when present in very low
concentrations.
• Hormones have powerful effects
when present in very low
concentrations.

Endocrine Glands Defined

• Exocrine glands
 when present in very low
concentrations.

Endocrine Glands Defined

• Exocrine glands
– Endocrine
secrete products Glands
into ducts which Defined
empty into body cavities or body
surface
•– Exocrine
sweat, oil,glands
mucous, & digestive glands
– secrete products into ducts which empty into body cavities or body
• Endocrine
surface glands
–
– secrete products
sweat, oil, mucous, (hormones) into
& digestive bloodstream
glands
– pituitary, thyroid, parathyroid, adrenal, pineal
•–
–
Endocrine
hypothalamus,
secrete
glands
products Loading…
thymus, pancreas,ovaries,testes, kidneys, stomach,
(hormones)
liver, small intestine, into
skin, heart bloodstream
& placenta
– pituitary, thyroid, parathyroid, adrenal, pineal
–
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hypothalamus, thymus, pancreas,ovaries,testes, kidneys, stomach,
liver, small intestine, skin, heart & placenta

Hormone Receptors 0

Hormone Receptors

• Hormones only affect target cells with specific membrane

proteins called receptors

• Hormones only affect target cells with specific membrane 0

proteins called receptors

Hormone Receptors
 • Hormones only affect target cells with specific membrane
proteins called receptors

• Hormones only affect target cells with specific membrane 0

proteins called receptors

Hormone Receptors

• Although hormones Hormone

travel in blood Receptors
throughout the body, they
affect only specific target cells.
•– Target cells
Although have specific
hormones protein
travel in orblood
glycoprotein receptorsthe
throughout to which
body, they
hormones bind.
affect only specific target cells.
•– Receptors are
Target cells constantly
have being
specific protein synthesized
or glycoprotein andtobroken
receptors which
down.
hormones bind.
• Receptors are constantly being synthesized and broken
down.

Regulation of Hormone Receptors

• Receptors are constantly being synthesized & broken
down Regulation of Hormone Receptors
– range of 2000-100,000 receptors / target cell
•• Receptors are constantly being synthesized & broken
Down-regulation
– down
excess hormone leads to a decrease in number of receptors
–• range of 2000-100,000
receptors receptors / target
undergo endocytosis and arecell
degraded
•– Down-regulation
decreases sensitivity of target cell to hormone
•– Up-regulation
excess hormone leads to a decrease in number of receptors
–• receptors
deficiency undergo endocytosis
of hormone and are degraded
leads to an increase in the number of receptors
–
– decreases
target tissue becomes more sensitivehormone
sensitivity of target cell to to the hormone
• Up-regulation
– deficiency of hormone leads to an increase in the number of receptors
– target tissue becomes more sensitive to the hormone

Circulating and Local Hormones

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Circulating and Local Hormones

Circulating and Local Hormones

• Hormones that travel in blood and act on distant target cells
are called circulating hormones or endocrines.
• Hormones that travel in blood
act locally andfirst
without act entering
on distant target
the bloodcells
are called
stream arecirculating
called localhormones
hormones. or endocrines.
•– Those thatthat
Hormones act on neighboring
act cells are called
locally without first paracrines.
entering the blood
– Those that act on the same cell that secreted them are termed autocrines.
stream are called local hormones.
– Those that act on neighboring cells are called paracrines.
– Endocrine
Those thathormones
act on
the same cell that secreted them are termed autocrines.
travel through blood
to reach target cell

Paracrines act on Autocrines act on the

neighboring cells cell that has
secreted them

Circulating & Local Hormones

Circulating & Local Hormones

• Circulating
hormones
• Circulating
Local hormones
– hormones
paracrines
– autocrines
• Local hormones
– paracrines
– autocrines

Chemical Classes of Hormones

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Chemical Classes of Hormones

Chemical Classes of Hormones

• Lipid-soluble hormones include the steroids, thyroid
hormones, and nitric oxide, which acts as a local hormone in
• several tissues.
Lipid-soluble hormones include the steroids, thyroid

•
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hormones, and nitric oxide, which acts as a local hormone in
several tissues.hormones include the amines; peptides,
Water-soluble

•
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proteins, and glycoproteins; and eicosanoids.
Water-soluble hormones include the amines; peptides,
proteins, and glycoproteins; and eicosanoids.

Lipid-soluble Hormones 0

•
Lipid-solubleSteroids
Hormones
– lipids derived from cholesterol on
SER
•– Steroids
different functional groups attached
– lipids
to corederived from cholesterol
of structure provide on
SER
uniqueness
– different functional groups attached
• Thyroid hormones
to core of structure provide
– uniqueness plus attached iodines
tyrosine ring
are lipid-soluble
• Thyroid hormones
•– Nitric oxide
tyrosine ringisplus
gasattached iodines
are lipid-soluble
• Nitric oxide is gas

Water-soluble Hormones 0

• Hormones
Water-soluble Amine, peptide and protein
 0

Water-soluble Hormones 0

• Hormones
Water-soluble Amine, peptide and protein
hormones
•– modified
Amine, amino acids
peptide andor protein
amino acids
put together
– hormones
serotonin, melatonin, histamine,
– modified amino acids or amino acids
epinephrine
– put
sometogether
glycoproteins
– serotonin, melatonin, histamine,
• Eicosanoids
epinephrine
–
– derived from arachidonic acid (fatty
some glycoproteins
acid)
•– Eicosanoids
prostaglandins or leukotrienes
– derived from arachidonic acid (fatty
acid)
– prostaglandins or leukotrienes

General Mechanisms of Hormone Action

Hormone
General bindsMechanisms
to cell surface or
ofreceptor
Hormone inside target cell
Action
Cell may then
• Hormone bindsnew
synthesize tomolecules
cell surface or receptor inside target cell
• change permeability of membrane
• Cell may
alter then
rates of reactions
• synthesize new molecules
• Each change
target permeability
cell responds to hormone differently
of membrane
• At liver
altercells---insulin stimulates glycogen synthesis
rates of reactions
At adipocytes---insulin stimulates triglyceride synthesis
Each target cell responds to hormone differently
At liver cells---insulin stimulates glycogen synthesis
At adipocytes---insulin stimulates triglyceride synthesis

Same hormone can act

differently on different
target cells

Action of Lipid-Soluble Hormone

 0

Action of Lipid-Soluble Hormone

• Action
Lipid-soluble of Lipid-Soluble
hormones Hormone
bind to and activate receptors
within cells.
•– The activated receptors
Lipid-soluble hormones then alter
bind gene
to expression which receptors
and activate results in the
formation of new proteins.
within cells.
–
– The
The activated receptors
new proteins then
alter the alter
cells gene and
activity expression
result inwhich results in the
the physiological
formation of new proteins.
responses of those hormones.

– The new proteins alter the cells activity and result in the physiological
On DNA we have a
responses of those hormones. sequence called hormone
response element HRE, the
Receptors for thyroid Steroids receptors hormone receptor complex
hormones are in the are in the cytoplasm attaches to HRE,making a
nucleus new mRNA ,which then
makes a new protein

Action of Lipid-Soluble Hormones 0

• Hormone
Action of Lipid-Soluble diffuses through
Hormones
phospholipid bilayer &
• into cell diffuses through
Hormone
• phospholipid
Binds bilayer
to receptor &
turning
into cell
on/off specific genes
• Binds to receptor
New mRNA turning
is formed &
on/off
directsspecific genes
synthesis of new
• proteins
New mRNA is formed &
• directs
New synthesis
protein altersofcell’s
new
proteins
activity
• New protein alters cell’s
activity

Action of Water-Soluble Hormones

 0

Action of Water-Soluble Hormones

• Actionhormones
Water-soluble of Water-Soluble Hormones
alter cell functions by activating
plasma membrane receptors, which set off a cascade of
• events inside the
Water-soluble cell.
hormones alter cell functions by activating
– The water-soluble
plasma membrane hormone that binds
receptors, to the set
which cell membrane receptorof
off a cascade is the
first messenger.
– events inside
A second the cell.
messenger is released inside the cell where hormone stimulated
– The water-soluble
response hormone that binds to the cell membrane receptor is the
takes place.
first
Aftermessenger.
hormone binds to
receptor with specific
– A second
information
messenger is released inside the cell where hormone stimulated
response takes place.
1st messenger 2nd messenger
(In the cell)

Categories of second messengers

Categories of second messengers
1. Cyclic nucleotides (cAMP; cGMP)
2. Ca2+
1.
3. Cyclic nucleotides
Phosphatidyl (cAMP; cGMP)
inositol
2.
4. Ca2+
Thyrosine Kinase
3. Phosphatidyl inositol
4. Thyrosine Kinase

Action of Water-Soluble Hormones

 Action of Water-Soluble Hormones

• The hormone Action bindsof to the membrane receptor.

Water-Soluble Hormones
• The activated receptor activates a membrane G-protein
• which
The turns onbinds
hormone adenylate cyclase. receptor.
to the membrane
• Adenylate
The activated cyclase
receptorconverts ATP ainto
activates cyclic AMP
membrane which
G-protein
activates
which turnsprotein kinases. cyclase.
on adenylate
• Protein kinases
Adenylate cyclase phosphorylate
converts ATP enzymes which
into cyclic AMPcatalyze
which
reactions protein
activates that produce kinases. the physiological response.
• Since hormones
Protein that bond to plasma
kinases phosphorylate enzymesmembrane receptors
which catalyze
initiate
reactions a cascade
that produce of events, they can induce
the physiological their effects at
response.
• very low
Since concentrations.
hormones that bond to plasma membrane receptors
Receptors are either stimulator or inhibitory
initiate a cascade of events, they can induce their effects at
very
Hormones low stimulator
are either concentrations.
or inhibitory

If hormone is S it binds to a S receptor

0

Action of Water-Soluble Hormones 0

• Can not diffuse through plasma

Action of Water-Soluble
membrane Hormones
• Hormone receptors are integral
• Can not diffuse
membrane through plasma
proteins
– membrane
act as first messenger
•• Hormone
The hormonereceptors
binds are
to theintegral
membrane
membrane
receptor. proteins
•– The act as firstreceptor
activated messenger activates a
• The
membrane G-protein whichmembrane
hormone binds to the turns on
receptor.
adenylate cyclase.
•• The activated
Adenylate receptor
cyclase activates
converts ATP ainto
membrane
cyclic AMP G-protein which protein
which activates turns on
adenylate
kinases. cyclase.
•• Adenylate cyclase
Protein kinases converts ATP
phosphorylate into
enzymes
cyclic
which AMP which
catalyze activates
reactions protein
that produce
kinases.
the physiological response.
• Protein kinases phosphorylate enzymes
which catalyze reactions that produce
the physiological response.

Active phosphorylase brakes down glycogen 0

increasing the amount of glucose.

Water-soluble Hormones 0

• Cyclic AMP is the 2nd

 which catalyze reactions that produce
the physiological response.

Water-soluble Hormones 0

• Cyclic
Water-soluble AMP is the 2nd
Hormones
messenger
•– kinases
Cyclic AMP in
is the
the cytosol
2nd
speed up/slow down
messenger
– physiological
kinases in the cytosol
responses
speed up/slow down
• physiological
Phosphodiesterase
responses
inactivates cAMP by
• inhibiting adenylate
Phosphodiesterase
cyclase
inactivates cAMP by
• inhibiting
Cell adenylate
response is turned off
cyclase
unless new hormone
• molecules
Cell arrive
response is turned off
unless new hormone
molecules arrive 0

cAM
P
cAM
P
 Second Messengers
• Some hormones exert their
Second influence by increasing the
Messengers
synthesis of cAMP
•– ADH, TSH, ACTH, glucagon and epinephrine
Some hormones exert their influence by increasing the
• Some exert
synthesis of their
cAMP influence by decreasing the level of cAMP
– growth hormone inhibiting hormone
– ADH, TSH, ACTH, glucagon and epinephrine
•• Other
Some substances
exert their can act as
influence by 2nd messengers
decreasing the level of cAMP
– calcium ions
– growth hormone inhibiting hormone
– cGMP
•• Other substances
A hormone can
may use act as 2nd
different 2nd messengers
messengers in different
– calcium ions
– target
cGMP cells
• A hormone may use different 2nd messengers in different
target cells

Amplification of Hormone Effects 0

 0

Amplification of Hormone Effects 0

• Amplification
Single of Hormone
molecule of hormone Effects
binds to receptor
• Activates 100 G-proteins
• Single moleculean
Each activates ofadenylate
hormone binds to molecule
cyclase receptor which
• Activates 100 G-proteins
then produces 1000 cAMP
• Each activates an adenylate
cAMP activates cyclase
a protein molecule
kinase, which
which may
then produces
act upon 1000’s1000 cAMP molecules
of substrate
• Each cAMP activates
One molecule a protein
of epinephrine kinase,
may resultwhich
in may
act upon 1000’s
breakdown of substrate
of millions molecules
of glycogen molecules into
• glucose
One molecules
molecule of epinephrine may result in
breakdown of millions of glycogen molecules into
glucose molecules

Cholera Toxin and G Proteins

• Toxin is Cholera
deadly because
Toxinit and
produces massive watery
G Proteins
diarrhea and person dies from dehydration
• Toxin is
of deadly
cholerabecause
bacteria itcauses
produces massive
G-protein to watery
lock in
diarrhea
activatedand person
state dies from
in intestinal dehydration
epithelium
• Toxin
Cyclicof
AMPcholera bacteria
causes causes
intestinal cellsG-protein to transport
to actively lock in
activated stateand
chloride (Na+ in intestinal epithelium
water follow) into the lumen
• Cyclic
PersonAMP causesions
die unless intestinal cellsare
and fluids to actively
replacedtransport
& receive
chloride
antibiotic(Na+ and water follow) into the lumen
treatment
• Person die unless ions and fluids are replaced & receive
antibiotic treatment

0
 0

Principles of Human Anatomy and Physiology, 11e

Phosphatidyl inositol 0

Phosphatidyl inositol
Inositol trisphosphate (IP3) and diacylglycerol
Principles of Human Anatomy and Physiology, 11e 0

(DAG)
Inositol trisphosphate (IP3) and diacylglycerol
Peptide and protein hormones like vasopressin, thyroid-
(DAG)
stimulating hormone (TSH), and angiotensin and
neurotransmitters
Peptide like
and protein GABA bind
hormones liketovasopressin,
G protein-coupled
thyroid-
receptors
stimulating(GPCRs)
hormonethat activate
(TSH), and the intracellular
angiotensin and
enzyme phospholipase
neurotransmitters like GABAC (PLC).
bind toAsGits name suggests, it
protein-coupled
hydrolyzes(GPCRs)
receptors phospholipids — specifically
that activate phosphatidylinositol-
the intracellular
4,5-bisphosphate (PIP2) which
enzyme phospholipase is found
C (PLC). As itsinname
the inner layer of
suggests, it the
plasma membrane.
hydrolyzes Hydrolysis
phospholipids of PIP2 yields
— specifically two products:
phosphatidylinositol-
diacylglycerol (DAG)
4,5-bisphosphate (PIP2) which is found in the inner layer of the
inositol-1,4,5-trisphosphate
plasma membrane. Hydrolysis(IP3) of PIP2 yields two products:
diacylglycerol (DAG)
inositol-1,4,5-trisphosphate (IP3)

Principles of Human Anatomy and Physiology, 11e 0

Principles of Human Anatomy and Physiology, 11e 0

diacylglycerol (DAG): DAG remains in the inner layer of the

plasma membrane. It recruits Protein Kinase C (PKC) —
 inositol-1,4,5-trisphosphate (IP3)

Principles of Human Anatomy and Physiology, 11e 0

Principles of Human Anatomy and Physiology, 11e 0

diacylglycerol (DAG): DAG remains in the inner layer of the

plasma membrane. It recruits Protein Kinase C (PKC) —
a calcium-dependent
diacylglycerol (DAG):kinase
DAG that phosphorylates
remains in the inner many
layer ofother
the
proteinsmembrane.
plasma that bring about the changes
It recruits in the cell.
Protein Kinase As its —
C (PKC) name
suggests, activation ofkinase
a calcium-dependent PKC requires calcium ions.many
that phosphorylates These are
other
made available
proteins by about
that bring the action of the other
the changes second
in the messenger
cell. As its name —
IP3.
suggests, activation of PKC requires calcium ions. These are
inositol-1,4,5-trisphosphate
made available by the action of(IP3):
diffuses
IP3.
the other Loading…
This soluble
second molecule
through the cytosol and binds to receptors on the
messenger —

endoplasmic reticulum causing(IP3):

inositol-1,4,5-trisphosphate
(Ca2+) into
diffuses the cytosol.
through The and
the cytosol
the release
rise binds
Loading…
of calcium
This soluble
in intracellular calcium
to receptors
ions
molecule
on thetriggers
the response.reticulum causing the release of calcium ions
endoplasmic
(Ca2+) into the cytosol. The rise in intracellular calcium triggers
the response.

Principles of Human Anatomy and Physiology, 11e 0

Principles of Human Anatomy and Physiology, 11e 0

Calmodulin dependent protein kinases:

These kinases are inactive until they bind calmodulin which has
4Calmodulin
calcium ions bound protein kinases:
dependent
Calmodulin
These kinases are inactive calcium
(intracellular until theybinding Proteins)which
bind calmodulin has 4 has
4calcium ions
calcium ionsbound,
boundit is bound by target proteins which activate
them..
Calmodulin (intracellular calcium binding Proteins) has 4
calcium ions bound, it is bound by target proteins which activate
them..

Principles of Human Anatomy and Physiology, 11e 0

Principles of Human Anatomy and Physiology, 11e 0

Principles of Human Anatomy and Physiology, 11e 0

Principles of Human Anatomy and Physiology, 11e 0

The Insulin Receptor

The Insulin Receptor

➢ Responsible for clearance of glucose
➢ In addition to binding insulin, it possesses a tyrosine
➢ Responsible
kinase activityfor clearance of glucose
➢ In
It isaddition
involvedto in
binding
many insulin,
cellular itactivities
possesses a tyrosine
kinase activity
➢ It is involved in many cellular activities
Insulin-mediated glucose transport signaling pathway
Insulin-mediated glucose transport signaling pathway
Insulin
Insulin-mediated glucose transport signaling pathway
Insulin-mediated glucose transport signaling pathway
IR a Insulin
a
b b
Cell membrane IR a a
b b
Cell membrane

P
IRS
PI3K

P
IRS
Glut4 PI3K
Akt
P

Glut4 Akt
P

Insulin-mediated glucose transport signaling pathway

Insulin-mediated glucose transport signaling pathway
 Glut4 Akt
P

Insulin-mediated glucose transport signaling pathway

Insulin-mediated glucose transport signaling pathway
Insulin-mediated glucose transport signaling pathway
Insulin-mediated glucose transport signaling pathway
IR Insulin
glucos a a
e b b Cell membrane
IR Insulin
glucos a a
e b b Cell membrane

P
IRS
PI3K

P
IRS
PI3K
Akt
P

Akt
P
Xiao Chen, 2006

Xiao Chen, 2006

Hormonal Interactions
• Hormonal
The responsiveness Interactions
of a target cell to a hormone depends
on the hormone’s concentration, the abundance of the target
• cell’sresponsiveness
The hormone receptors, and influences
of a target exerted by
cell to a hormone other
depends
hormones.
on the hormone’s concentration, the abundance of the target
• cell’s hormone
Three hormonalreceptors, andare
interactions influences
the exerted by other
– hormones.
permissive effect
– synergistic effect
•– Three hormonal
antagonist effectinteractions are the
– permissive effect
– synergistic effect
– antagonist effect

Hormonal Interactions 0

• Permissive effect
 0

Hormonal Interactions
• Permissive effect
– a second hormone, strengthens the effects of the first
– thyroid strengthens epinephrine’s effect upon lipolysis
• Synergistic effect
– two hormones acting together for greater effect
– estrogen & LH are both needed for oocyte production
• Antagonistic effects
– two hormones with opposite effects
– insulin promotes glycogen formation & glucagon stimulates glycogen
breakdown

0
 Hypothalamus and Pituitary
• The hypothalamus-pituitary unit is the most
dominant portion of the entire endocrine system.
• The output of the hypothalamus-pituitary unit
regulates the function of the thyroid, adrenal and
reproductive glands and also controls somatic
growth, lactation, milk secretion and water
metabolism.

Hypothalamus and Pituitary

• Pituitary function depends on the hypothalamus

and the anatomical organization of the
hypothalamus-pituitary unit reflects this
relationship.
• The pituitary gland lies in a pocket of bone at the
base of the brain, just below the hypothalamus
to which it is connected by a stalk containing
nerve fibers and blood vessels. The pituitary is
composed to two lobes-- anterior and posterior
 The pituitary gland
HYPOTHALAMUS
Hypothalamus secretes ADH & oxytocin carried from
releasing factors hypothalamus

INFUNDIBULUM

Thyroid stimulating
hormone
Adrenocorticotropic
hormone
Antidiuretic hormone
Gonadotropic hormones
ANTERIOR POSTERIOR Oxytocin
(FSH & LH)
LOBE LOBE
Growth hormone
Prolactin
 Posterior pituitary gland

General Functions of the hypothalamus

1. Controls body temperature.

2. Controls the cardiovascular system.
3. Controls food intake & body weight.
4. Controls thirst & water balance.
5. Involved in sleep & wakefulness.
6. Involved in emotional reactions.
7. Involved in reactions to stress.
8. Controls ovarian secretions during ovarian cycle.
9. Controls testicular secretions.
 Hypothalamus Releasing Hormones:
Secretion

• Is influenced by emotions
• Can be influenced by the metabolic state of the
individual
• Delivered to the anterior pituitary via the
hypothalamic-hypophyseal portal system

Hypothalamic Releasing Hormones

Seven releasing hormones are made in the hypothalamus

– Thyrotropin-releasing hormone (TRH)
– Corticotropin-releasing hormone (CRH)
– Gonadotropin-releasing hormone (GnRH)
– Growth hormone-releasing hormone (GHRH)
– Growth hormone-release inhibiting hormone (GHIH)
– Prolactin-releasing factor (PRF)
– Prolactin-inhibiting hormone (PIH)
 Releasing Hypothalamus Nervous
hormones

Anterior pituitary Posterior pituitary

Thyrotropin
Somatotropin FSH Vasopressin

LH Prolactin Oxytocin
ACTH

Adrenal Adrenal
Thyroid Cortex Pancreas Ovary Testis Medulla

T3 Cortisol Insulin, Estradiol Testosterone Epinephrine

aldosterone glucagon,
somatostatin

Muscles Liver, Reproductive Mammary

liver Tissues muscles organs glands

Hypothalamic hormones

Hypothalamus

GnRH GHRH GHIH/SS TRH PRIH PRH CRH

+ + - - + + - + +
FSH & LH GH TSH Prolactin ACTH
Anterior Pituitary
 The Pituitary gland (hypophysis):

 Small gland ( 1cm diameter;  0.5 to 1 gm weight).

 Lies in sella turnica, a bony cavity at the base of the brain.
 Connected to the hypothalamus by the pituitary stalk or
(hypophysial; infundibulum).

 Structurally & functionally

divided into 2 lobes:

1) Anterior lobe (2/3),

2) Posterior lobe (1/3).

Anterior Pituitary

Is also called the Adenohypophysis

Secretes tropic hormones in a pulsatile fashion
Synthesizes various hormones in various specific cell
populations
 Anterior Pituitary Hormones

Each of anterior pituitary hormone is synthesized

by a cell population.
Corticotropes - ACTH
Lactotropes - Prolactin
Somatotropes - GH
Thyrotropes - Thyrotropin
Gonadotropes - FSH, LH

Anterior pituitary: adenohypophysis

• Anterior pituitary: connected to the hypothalamus

by the superior hypophyseal artery.
• The anterior pituitary produces six peptide
hormones:
• prolactin
• growth hormone (GH)
• thyroid stimulating hormone (TSH)
• follicle-stimulating hormone (FSH)
• luteinizing hormone (LH)
• adrenocorticotropic hormone (ACTH)
 Anterior Pituitary Hormones
Growth Hormone (GH, Somatotropin): primary hormone responsible for
regulating body growth, and is important in metabolism
Thyroid-stimulating Hormone (TSH): stimulates secretion of thyroid
hormone & growth of thyroid gland
Adrenocorticotropic Hormone (ACTH): stimulates cortisol secretion by the
adrenal cortex & promotes growth of adrenal cortex
Follicle-stimulating Hormone (FSH): Females: stimulates growth &
development of ovarian follicles, promotes secretion of estrogen by ovaries.
Males: required for sperm production
Luteinizing Hormone (LH): Females: responsible for ovulation, formation of
corpus luteum in the ovary, and regulation of ovarian secretion of female sex
hormones. Males: stimulates cell in the testes to secrete testosterone
Prolactin: Females: stimulates breast development and milk production.
Males: involved in testicular function

HYPOTHALAMIC EFFECTS ON THE

HORMONE ANTERIOR PITUITARY
Thyrotropin-releasing hormone Stimulates release of TSH
(TRH) (thyrotropin) and Prolactin
Corticotropin-releasing hormone Stimulates release of ACTH
(CRH) (corticotropin)
Gonadrotropin-releasing Stimulates release of FSH and
hormone (GnRH) LH (gonadotropins)
Growth hormone-releasing Stimulates release of growth
hormone (GHRH) hormone
Growth hormone-inhibiting Inhibits release of growth
hormone (GHIH) hormone
Prolactin-releasing hormone Stimulates release of prolactin
(PRH)
Prolactin-inhibiting hormone Inhibits release of prolactin
(PIH)
 Anterior Pituitary Hormones

Hormones Target Principal action

tissue
1. Growth hormone Most (+) protein synthesis & growth;
(GH, or somatotropin) tissue lipolysis; bl glucose

2. Thyroid-stimulating hormone Thyroid (+) thyroid hormones

(TSH, or thyrotropin) gland
3. Adrenocorticotropic hormone Adrenal (+) glucocorticoids
(ACTH, or corticotrophins) cortex
4. Follicle-stimulating hormone Gonads (+) gamete production, (+)
(FSH, or folliculotropin) estrogen in ♀

5. Luteinizing hormone Gonads (+) sex hormones; ovulation &

(LH, or luteotropin) corpus luteum formation in
females; (+) testosterone in ♂
6. Prolactin (PRL) Mammary (+) milk in lactating ♀; regulates ♂
glands reproductive system
 Anterior Pituitary Hormones

Anterior pituitary hormones

Anterior Pituitary

FSH & LH GH TSH Prolactin ACTH

+ + + + +
Thyroid Mammary Adrenal
Gonads Most tissues
gland glands cortex

 estrogen;
 protein synthesis; + T4; + milk;  glucocorticoids
progeterone;
 Lipolysis; & + T3 + breast dvlp.
+ testosterone
 blood glucose + thyroid regulate ♂
+ gametes; growth reproductive
+ ovulation; system
 ACTH synthesis

ACTH

Processing and cleavage of pro-opiomelanocortin (POMC)

ACTH
 ACTH is made up of 39 amino acids
 Regulates adrenal cortex and synthesis of
adrenocorticosteroids
 -MSH resides in first 13 aa of ACTH
 -MSH stimulates melanocytes and can darken skin
 Overproduction of ACTH may accompany increased
pigmentation due to -MSH.
 -endorphin

• Produced as a result of ACTH synthesis

• Binds to opiate receptors
• Results in “runner’s high”
• Role in anterior pituitary not completely understood
• One of many endogenous opioids such as
enkephalins

Melanocyte-stimulating hormone
(MSH)

• MSH peptides derived by proteolytic cleavage of

POMC
• -MSH has antipyretic and anti-inflammatory effects
• Four MSH receptors identified
• May inhibit feeding behavior • Può inibire il comportamento alimentare

• ACTH has MSH-like activity

• However– MSH has NO ACTH like activity
 Posterior Pituitary: neurohypophysis

• Posterior pituitary:
• An outgrowth of the hypothalamus composed of neural
tissue.
Hypothalamic neurons pass through the neural stalk and
end in the posterior pituitary. Hormones synthesized in
the hypothalamus are transported down the axons to the
endings in the posterior pituitary.
Hormones are stored in vesicles in the posterior pituitary
until release into the circulation
Principal Hormones: Vasopressin & Oxytocin

Posterior Pituitary

Comprised of the endings of axons from cell bodies in the

hypothalamus (supraoptic and paraventricular)
Axons pass from the hypothalamus to the posterior pituitary via
the hypothalamohypophysial tract
Posterior pituitary hormones are synthesized in the cell bodies
of neurons in the supraoptic and paraventricular nuclei
 posterior pituitary gland

Secretion of Posterior Pituitary Hormones

om

Figure 7-12: Synthesis, storage, and release of posterior pituitary hormones

 Posterior pituitary hormones:
ADH (VP) and Oxytocin
 Both are synthesized in the cell bodies of
hypothalamic neurons
 ADH: supraoptic nucleus
 Oxytocin: paraventricular nucleus
 Both are synthesized as preprohormones and
processed into nonapeptides (nine amino acids).
 They are released from the termini in response to an
action potential which travels from the axon body in
the hypothalamus

Structures of ADH and oxytocin

 Oxytocin:
Stimulates myoepithelial contractions

 In uterus during parturition(Child Birth)

 In mammary gland during lactation

Oxytocin:
Milk ejection from lactating mammary gland

 sucking is major stimulus for release.

 sensory receptors in nipple connect with nerve fibers to
the spine, then impulses are relayed through brain to
paraventricular nucleus where cholinergic synapses fire on
oxytocin neurons and stimulate release.
 Oxytocin
Uterine contractions

• Reflexes originating in the cervical, vaginal and

uterus stimulate oxytocin synthesis and release via
neural input to hypothalamus
• Increases in plasma at time of ovulation, parturition,
and coitus

ADH
Conserve body water and regulate tonicity of
body fluids

 Also known as vasopressin

 Regulated by osmotic and volume stimuli
 Water deprivation increases osmolality of
plasma which activates hypothalmic
osmoreceptors to stimulate ADH release
 Feedback Loops

Hypothalamus

Anterior
Pituitary
Corticotropin
Adrenal
releasing factor
+ Cortex

-Corticotropin

Cortisol

Feedback Control of the Anterior Pituitary

• Short feedback
loop:
– Retrograde transport of
blood from anterior
pituitary to the
hypothalamus.
• Hormone released by
anterior pituitary
inhibits secretion of
releasing hormone.

• Positive feedback
effect:
– During the menstrual
cycle, estrogen
stimulates “LH surge.”
Hormones of the Adrenal Cortex

0
 Adrenal Glands
The outer part is called the adrenal cortex, which
produces many different hormones called
corticosteroids. This includes cortisol. These
hormones regulate the salt and water balance in the
body, prepare the body for stress, regulate
metabolism, interact with the immune system, and
induce sexual function.

The inner part, which is called the adrenal medulla,

produces
catecholamines, such as epinephrine. Epinephrine
also known as adrenaline, increase the blood pressure
and heart rate during times of stress.
0

Adrenal Glands

0
 Hormones of adrenal cortex
Three general classes of steroid hormones based on predominant functions

Mineralocorticoids: 21 carbon containing steroids ,

synthesized by zona glomerulosa, regulate
water and electrolyte balance. Aldosterone is
the most prominent mineralocorticoid.

Glucocorticoids: Also 21 carbon steroids, produced mostly

in zona fasciculata and affect glucose (hence
the name), amino acid and fat metabolism.
Cortisol (also known as hydrocortisone) is most
important GC in humans.

Androgens: The zona reticularis and fasciculata produce

significant amounts of androgen precursor
DHEA (dehydroepiandrosterone) and
androstenedione (both 19 carbon).
0

Synthesis of Adrenocortical Hormones

• Made from cholesterol taken from LDLs in the blood and
stored in adrenocortical cells

• Adrenocortical cells stimulated by ACTH or cAMP.

Cholesterol

0
 Synthesis of Adrenocortical Hormones

Synthesis of Adrenocortical Hormones

0
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 Storage and Secretion

• Little (if any) storage of steroid hormones , directly

go into circulation as and when they are produced
• Cortisol release follows the diurnal rhythm of
ACTH release. Highest levels in the morning
shortly after awakening and lowest in the evening
and early morning.

Plasma Transport
• Cortisol circulates in plasma bound to proteins
or as free.
• Transcortin or corticosteroid binding globulin (CBG)
binds cortisol.
• Most of the steroid hormones bind to CBG.
• Cortisol binds CBG and has a half life of 1.5 - 2
hrs. 8-10% Cortisol is free.

• Progesterone and deoxycorticosterone also bind

CBG strongly.
• Corticosterone binds CBG with less affinity.
• Aldosterone does not have a specific protein but
binds weekly with albumin
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 Degradation and Excretion
• Glucocorticoids: Cortisol, Cortisone and 11-
deoxycortosol are reduced by NADPH dependant
enzymes and conjugated with either glucoronate or
sulfate which render them water soluble. About 70%
of the conjugated steroids are excreted in the urine ,
20% in feces and rest exit through the skin.
• Mineralocorticoids: Aldosterone is very rapidly
cleared from the plasma by liver because it lacks a
specific protein carrier. It is converted to
tetrahydroaldosterone 3-glucoronide which is
excreted in urine.
• Androgens: are excreted as 17-keto compounds
including DHEA (sulfate) as well as androstenedione
and its metabolites. Small amounts of testosterone
secreted by adrenals are also converted to 17-keto
compounds like androsterone and etiocholanolone
which are excreted in urine. 0

Metabolic functions of corticosteroids

Glucocorticoid hormones: the most important are

Cortisol, cortisone and Corticosterone
• Effects on Carbohydrate metabolism:
• ↑es Gluconeogenesis and glucose output
• ↑es amino acid utilization
• ↑es glycogen storage
• ↓es glucose uptake by tissues other than liver
• Effects on Lipid metabolism:
• ↑es lipolysis
• ↑es circulating free fatty acids (FFA)
• ↓ es utilization of FFA for TG synthesis.
0
• Effects on Protein metabolism:
• ↑es degradation of proteins in extra hepatic tissues
• ↑es protein synthesis in liver
• Effects on Nucleic acid metabolism:
• promotes transcription of specific genes in liver.
• Effects on water and electrolyte metabolism:
• Mediated through ADH , causes decrease in ADH
• Other biochemical functions:
• Suppress immune response in high doses (esp. cortisol)
• Modulate response of catecholamines

Hormones of the Adrenal Cortex

0
 Metabolic functions of adrenocorticosteroids

Androgens: DHEA and androstenedione are

precursors of testosterone which is the most potent
androgen. General Biochemical functions of androgens
are:
• Growth, development and maintenance of male
reproductive organs
• Effect on protein metabolism: promote protein
synthesis , positive nitrogen balance and increase
muscle mass.

• Effect on carbohydrate and fat metabolism:

increase glycolysis, lipolysis and TCA cycle

• Effect on mineral metabolism: Promote mineral

deposition and bone growth.
0

Metabolic functions of adrenocorticosteroids

Mineralocorticoid hormones: The most active and

potent mineralocorticoid is Aldosterone.

• ↑es reabsorption of sodium by the distal

convoluted tubules of kidney. Water follows
sodium , thus leads to water retention

• ↑es Excretion of K+, H+ and NH+4 ions in urine.

• Acts on all epithelial cells that exchange Na and

water( kidney , GI tract , salivary glands etc)

• Promotes synthesis of transport proteins (pumps)

which facilitate Na and water movement across
cell membranes. 0
Hormones of the Adrenal Cortex

Hormones of Adrenal medulla

chromaffin cells produce

Adrenaline
Noradrenaline
 Catecolamine hormones:
Water soluble compound epinephrine and
norepinephrine; produced in brain as neurotransmitter
and in endocrine hormone in adrenal gland; stored
secretary vesicle; exocytosis; bind to receptor;
generate second messenger

Hormones of medulla - catecholamines

• Epinephrine, norepinephrine and DOPA

• Nature – derivatives of tyrosine
• Excretion is regulated by sympathetic nervous system
and brain cortex

Epinephrine Norepinephrine
Stress and The Adrenal Glands

Functions of catecholamines:

Stress hormones. Contraction of vessels, increase the blood

pressure, accelerate pulse. Contraction of uterus muscles.
Epinephrine relaxes the muscles of bronchi and intestine.
On carbohydrate metabolism:
-activates the decomposition of glycogen in liver and muscles
-activates glycolysis, TAC and tissue respiration
On protein metabolism
-accelerate the decomposition of proteins
On lipid metabolism
-activates lipase, mobilization of lipids and their oxidation
 Adrenal medulla :
Hyper secretion of the adrenal medulla
caused by a tumor (pheochromocytoma)
results in excessive secretion of
catecholamines, of which 80% is epinephrine
and the remainder is norepinephrine

DISORDERS OF THE ADRENAL GLAND

ADRENAL GLAND HYPOFUNCTION
• (Addisons Disease
Insufficiency )
of adrenocortical steroids causes problems
through the loss of mineralocorticoid (aldosterone) and
glucocorticoid (cortisol) action
• Impaired secretion of cortisol results :in decreased
gluconeogenesis, leading to hypoglycemia. The
glomerular filtration rate and gastric acid production
decrease, leading to a reduction in urea nitrogen excretion,
causing anorexia and weight loss
• Reduced aldosterone secretion causes potassium, sodium,
and water imbalances. Potassium excretion is
decreased,causing hyperkalemia; sodium and water
excretion is increased, causing hyponatremia and
hypovolemia. Potassium retention also promotes
reabsorption of hydrogen ions, which can ultimately lead to
acidosis
 DISORDERS OF THE ADRENAL GLAND
ADRENAL GLAND HYPOFUNCTION
Addison crisis
• Acute adrenal insufficiency, or Addison crisis, is
a life threatening event in which the physiologic
need for glucocorticoid and mineralocorticoid
hormones is greater than the available supply

• In most cases, acute adrenal insufficiency occurs

in response to a stressful event (e.g., surgery,
trauma, or severe infection.

DISORDERS OF THE ADRENAL GLAND

HYPERFUNCTION (Cushing's syndrome)
• Hypersecretion by the adrenal cortex may result in
excessive amounts of glucocorticoids, leading to
hypercortisolism (e.g., Cushing's syndrome),
hyperaldosteronism (excessive mineralocorticoid
production), or excessive androgen production
 DISORDERS OF THE ADRENAL GLAND
PERFUNCTION
• The client with Cushing's syndrome has alterations of nitrogen,
carbohydrate, and mineral metabolism. An increase in total
body fat results from slow turnover of plasma fatty acids, and a
redistribution of fat produces the typical body pattern of trancal
obesity, "buffalo hump," and "moon face“
• Increases in the breakdown of tissue protein and an increase in
urine nitrogen excretion also occur, resulting in decreased
muscle mass, atrophic (thin) skin, and bone density loss
• High levels of corticosteroids kill lymphocytes and shrink
organs containing lymphocytes, such as the liver, the spleen,
and the lymph nodes. Thus protection of the inflammatory and
immune responses is reduced .Reddish purple striae
("stretch marks") are often present on the abdomen,
upper thighs, and upper arms because of the
degradative effect of cortisol on collagen

DISORDERS OF THE ADRENAL GLAND

HYPERFUNCTION
• In most cases, increased androgen production
causes acne, hirsutism (increased hair growth),
and occasionally, clitoral hypertrophy
• Increased androgen production can also interrupt
the normal hormone feedback mechanism for the
ovary, decreasing the ovary's production of
estrogens and progesterone. Oligomenorrhea
(scant or infrequent menses) occurs as a result
 DISORDERS OF THE ADRENAL GLAND
HYPERFUNCTION
Hyperaldosteronism
• In clients with hyperaldosteronism, increased secretion
of aldosterone results in mineralocorticoid excess.
• Primary hyperaldosteronism (Conn's syndrome) is due
to excessive secretion of aldosterone from one or both
adrenal glands, which is most commonly caused by an
adenoma.
• In a person with secondary hyperaldosteronism, the
continuous excessive secretion of aldosterone is caused
by high levels of angiotensin II that are due to high
plasma renin activity. Causes of this renin activation
include renal hypoxemia and the use of thiazide
diuretics.

DISORDERS OF THE ADRENAL GLAND

HYPERFUNCTION
• Increased aldosterone levels affect the renal
tubules and cause sodium retention with
potassium and hydrogen ion excretion.

• Hypernatremia, hypokalemia, and metabolic

alkalosis result.

• Sodium retention increases blood and interstitial

fluid volume, which elevates blood pressure and
suppresses renin production. The elevated blood
pressure may cause strokes and renal damage.
 DISORDERS OF THE ADRENAL
GLAND HYPERFUNCTION
Pheochromocytoma
• Pheochromocytoma is a catecholamine-producing
tumor that arises in chromaffin cells
• Pheochromocytomas release the catecholamines
epinephrine and norepinephrine (NE). Excessive
epinephrine and NE stimulate alpha receptors and
beta receptors and can have wide-ranging adverse
effects mimicking stimulation of the sympathetic
division of the autonomic nervous system

Clinical features of Cushing’s syndrome

Signs and symptoms associated with Cushing’s
syndrome vary but frequently include:

Obesity in the torso with thinner arms and legs

Large rounded face (moon face)

Increased fat in the neck and shoulder area
Thin fragile skin that bruises easily and heals
slowly.
Purplish streaks that look like stretch marks on
their abdomen, thighs, and buttocks.
Muscle weakness
Osteoporosis
High blood pressure
Increased blood sugar
DISORDERS OF THE ADRENAL GLAND
HYPERFUNCTION
 Thyroid
gland
Thyroid
gland

A butterfly-shaped organ, the thyroid gland is located anterior to the

trachea, just inferior to the larynx . The medial region, called the
isthmus,
A is flanked organ,
butterfly-shaped by wing-shaped
the thyroid leftgland
and right lobes.anterior
is located Each oftothe
the
thyroid lobes
trachea, are embedded
just inferior with parathyroid
to the larynx . The medialglands,
region,primarily
called theon
their posterior
isthmus, surfaces.
is flanked The tissue ofleft
by wing-shaped theand
thyroid
right gland
lobes.isEach
composed
of the
mostly
thyroid of thyroid
lobes follicles. The
are embedded withfollicles are made
parathyroid up of
glands, a central
primarily on
cavityposterior
their filled with a sticky
surfaces. fluid
The called
tissue colloid.
of the Surrounded
thyroid by a wall
gland is composed
of epithelial
mostly follicle
of thyroid cells, the
follicles. Thecolloid is the
follicles arecenter
made ofup thyroid
of a central
hormone
cavity production,
filled and that
with a sticky fluidproduction is dependent
called colloid. on the
Surrounded by a wall
hormones’
of epithelialessential and unique
follicle cells, component:
the colloid iodine.of thyroid
is the center
hormone production, and that production is dependent on the
hormones’ essential and unique component: iodine.
 Loading…

Chemistry of Thyroid Hormones

Thyroid hormones are derivatives of the the amino acid tyrosine
bound covalently to iodine. The two principal thyroid hormones
are:
thyroxine (also known as T4 or L-3,5,3',5'-tetraiodothyronine)
triiodothyronine (T3 or L-3,5,3'-triiodothyronine)
A large majority of the thyroid hormone secreted from the
thyroid gland is T4, but T3 is the considerably more active The
principle carrier of thyroid hormones is thyroxine-binding
globulin, a glycoprotein synthesized in the liver. Two other
carriers of import are transthyrein and albumin.
 Loading…

SYNTHESIS AND RELEASE OF THYROID

HORMONES
Hormones are produced in the colloid when atoms of the mineral
iodine attach to a glycoprotein, called thyroglobulin, that is secreted
into the colloid by the follicle cells.
Binding of TSH to its receptors in the follicle cells of the thyroid
gland causes the cells to actively transport iodide ions (I–) across
their cell membrane, from the bloodstream into the cytosol. As a
result, the concentration of iodide ions “trapped” in the follicular
cells is many times higher than the concentration in the bloodstream.
Iodide ions then move to the lumen of the follicle cells that border the
colloid. There, theo ions undergo oxidation (their negatively charged
electrons are removed). The oxidation of two iodide ions (2 I–)
results in iodine (I2), which passes through the follicle cell membrane
into the colloid
results inThere,
colloid. iodinethe
(I2), which
ions passes
undergo through(their
oxidation the follicle cell membrane
negatively charged
into the colloid
electrons are removed). The oxidation of two iodide ions (2 I–)
results in iodine (I2), which passes through the follicle cell membrane
into the colloid

• Thyroid Follicle

• Thyroid Follicle

In the colloid, peroxidase enzymes link the iodine to the tyrosine

amino acids in thyroglobulin to produce two intermediaries: a
In the colloid, peroxidase enzymes link the iodine to the tyrosine
amino acids in thyroglobulin to produce two intermediaries: a
tyrosine attached to one iodine and a tyrosine attached to two
iodines. When one of each of these intermediaries is linked by
covalent bonds, the resulting compound is triiodothyronine (T3), a
thyroid hormone with three iodines. Much more commonly, two
copies of the second intermediary bond, forming
tetraiodothyronine, also known as thyroxine (T4), a thyroid
hormone with four iodines.
These hormones remain in the colloid center of the thyroid follicles
until TSH stimulates endocytosis of colloid back into the follicle
cells. There, lysosomal enzymes break apart the thyroglobulin
colloid, releasing free T3 and T4, which diffuse across the follicle
cell membrane and enter the bloodstream

Thyroid hormone regulates the basal metabolic rate and is

important for growth and development. Thyroid hormone is
particularly important for brain development, but hypothyroidism
(low thyroid hormone) also leads to decreased muscle mass and
skeletal development.

The main activity of the thyroid hormones T3 and T4 is to boost

the basal metabolic rates of proteins, fats, and carbohydrates as
well as vitamins.
Hyperthyroidism occurs when the thyroid gland produces
excessive amounts of thyroid hormones. The most common cause of
hyperthyroidism is Graves’ disease. Graves’ disease is an
autoimmune disorder in which abnormal antibodies produced by the
immune system stimulate the thyroid to secrete excessive quantities
of its hormones . Graves’ disease often results in the formation of an
enlarged thyroid (goiter) because of the continued stimulation to
produce more hormones. Loading…
Other causes of hyperthyroidism include:
- excess iodine, a key ingredient in T4 and T3
- thyroiditis, or inflammation of the thyroid, which causes T4 and T3
to leak out of the gland
- tumors of the ovaries or testes
- benign tumors of the thyroid or pituitary gland
- large amounts of tetraiodothyronine taken through dietary
supplements or medication
.

Besides a goiter, other signs and symptoms of hyperthyroidism

may include protruding eyes(exophthalmos), a condition that’s
related to Graves’ disease., heart palpitations, excessive sweating,
diarrhea, weight loss despite increased appetite, muscle weakness,
and unusual sensitivity to heat. Medications can be prescribed to
mitigate the symptoms of the disease
Hypothyroidism occurs when the thyroid gland produces
insufficient amounts of thyroid hormones. It can result from surgical
Hypothyroidism
removal of the thyroid or dietary
occurs wheniodine deficiency.
the thyroid gland In cases of
produces
iodine deficiency,
insufficient amountstheofnegative
thyroid feedback
hormones. loop controlling
It can the surgical
result from release
of thyroidofhormone
removal causes
the thyroid repeated
or dietary stimulation
iodine of the
deficiency. thyroid.
In cases of This
results deficiency,
iodine in the thyroid
thegland growing
negative in size
feedback andcontrolling
loop producingthe a goiter
release
Other
of cause
thyroid of hypothyroidism
hormone is Hashimoto’s
causes repeated stimulation thyroiditis. This
of the thyroid. is
This
anotherinautoimmune
results the thyroid disease, but in this
gland growing case,
in size andtheproducing
immune system
a goiter
destroys the of
Other cause thyroid gland, producing
hypothyroidism hypothyroidism.
is Hashimoto’s thyroiditis. This is
Hypothyroidism
another autoimmune produces many
disease, butsigns
in thisand symptoms
case, suchsystem
the immune as
abnormalthe
destroys weight gain,
thyroid tiredness,
gland, baldness,
producing cold intolerance, and
hypothyroidism.
slow heart rate. Hypothyroidism
Hypothyroidism produces many signs is generally treated with
and symptoms suchthyroid
as
hormone replacement
abnormal weight gain,therapy.
tiredness, baldness, cold intolerance, and
slow heart rate. Hypothyroidism is generally treated with thyroid
hormone replacement therapy.

Regulation of thyroid
hormones
The pituitary gland and hypothalamus both control the thyroid. When
thyroid hormone
Regulation oflevels drop too low, the hypothalamus secretes TSH
thyroid
Releasing Hormone (TRH), which alerts the pituitary to produce thyroid
hormones
The pituitary gland and hypothalamus both control the thyroid. When
stimulating hormone (TSH). The thyroid responds to this chain of events
thyroid hormone levels drop too low, the hypothalamus secretes TSH
by producing more hormones
Releasing Hormone (TRH), which alerts the pituitary to produce thyroid
stimulating hormone (TSH). The thyroid responds to this chain of events
by producing more hormones

Feedback loops are used extensively to regulate secretion of hormones in the

hypothalamic-pituitary axis. When large amounts of hormones thyroxine
Feedback loops are used extensively to regulate secretion of hormones in the
hypothalamic-pituitary axis. When large amounts of hormones thyroxine
and triiodothyronine (T4 and T3) are synthesized and secreted by thyroid
glands inhibition of TRH secretion by large loop leads to shut-off of TSH
secretion, which leads to shut-off of thyroid hormone secretion. As thyroid
hormone levels decrease below the threshold, negative feedback is relieved,
TRH secretion starts again, leading to TSH secretion.