Endocrine

EndocrinephysiologyEndocrinephysiology
Outline
1) Hormones: the
basics
2) Hormones: types
and mechanisms
3) Endocrine organs (covered in course)
hypothalamus
anterior and
posterior
pituitary
the
adrenal
glands
pancreas
kidney
HKin
191
Key
concepts:
Hormones
vs. nerves as communication systems
Types of hormones: structural
and functional definitions
How
hormone structure
affects
mode of action
Why hormones
need receptors to work
How the same hormone can cause different responses
How the nervous and endocrine systems
are
integrated
HKin
191
Control
systems
growth and development

response
adaptation
require
communication
maintenance of homeostasis
reproduction
neural systemendocrine system
body
HKin
191
1)
Hormones:
the
basics
HKin191MediatorsTargetsRangeDurationSpeedofactionCharacteristicAlltypesofcellsmu
scle,glandular,andneuralcellsHormonesNeurotransmittersSystemicbutregulatedLocalL
ong(seconds-days)Short(milliseconds)
Slow(seconds-days)Fast(milliseconds)
HormonalcontrolNeuralcontrol
2)
Hormones:
types
and
mechanisms
four
functional
types
i)
local
hormones
ii)
iii)
circulating hormones
iv)
HKin
191
HKin 191
Endocrine physiology
6
1) Paracrine: cell-to-cell communication (local hormone)
Cardiomyocyte
b1-adrenergic
receptor
e.g. movement of epinephrine across a synapse
Endocrine physiology Endocrinephysiology
2) Autocrine: intra-cell communication (local)
e.g.
T-cell
activation
and
proliferation
antigensIl-2(fromhelperT-cells)
antigenpresentingcellactivatedT-cellsT-cellproliferativeT-cellsforexampleonly:yo
uarenotresponsibleforthismaterial
HKin
191
HKin 191
8
3) Neurocrine: nerve mediated hormonal communication
e.g. antidiuretic hormone (ADH)

hypothalamus posterior pituitary gland bloodstream
neurocrine endocrine
4) Endocrine: intercellular
communication (circulatory)
e.g.atrialnateureticfactorreleasedfromatriainresponsetomorestretchANFbindstokidn
eyreceptorsinurineproductionreducestretchANF
HKin
191
Hormones:
types
and
mechanisms
(see table 18.2)
Two basic chemical
families
amine
hormones
e.g.
epinephrine
subtypes
peptide
hormones
e.g.
ANF
eicosanoid
hormones
e.g.
leukotrienes
HKin191 steroidhormonese.g.cortisol thyroidhormonese.g.T3 nitricoxide(NO)
subtypes
Endocrine
physiology
Water soluble hormones cannot
enter cells
HKin
191
Signal transduction
pathways of
water soluble
hormones
hormonereceptorcellmembraneinactiveGproteinactiveGproteininactiveeffectoractivee
ffector(e.g.adenylatecyclase)
lowconcentration2ndmessengerhighconcentration2ndmessenger(e.g.cAMP)
inactivetargetactivetargetadaptedfromBerneandLevy2000(for191,youshouldknowthepri
ncipleandexistenceofthiscascade,youarenotresponsibleforthedetails)
HKin
191
EndocrinephysiologyFat soluble hormones canentercellsEndocrinephysiologyFat solu
ble hormones canentercells
hormone
binds
to
receptor
hormone:
receptor
complex
binds
to
DNA
activated
receptor
acts
as
transcription
factor
up/down
regulates
genes
with
appropriate
regulatory
sequences
HKin
191
Gene
activation
pathways of fat soluble
hormones
HKin191
EndocrinephysiologyGeneactivationpathways of fat solublehormonesEndocrinephysiol
ogyGeneactivationpathways of fat solublehormones
Hormone:
receptor
complex (acting as transcription
factor)
DNAstimulatestranscription
response element
regulated gene
(specific DNA sequence)
HKin
191
Endocrinephysiology163)Endocrineorgansthe hypothalamus
Endocrinephysiology163)Endocrineorgansthe hypothalamus
releases
controlling
hormones
to
_____________________
releases
ADH
and
oxytocin
to
_______________________
HKin
191
Input
limbic systeme.g.emotion,
fright,
smelloptic systemsightreticularactivating
substancee.g. sleep/wakethalamuspainTemperatureRegulation

EnergyRegulatione.g.hunger, satiety, body mass

Autonomicregulatione.g.blood pressure, HR(Forgeneralinterestonly,youdonothavetom
emorizethis)
AdaptedfromBerneandLevy,2000)
posteriorpituitarywaterbalancelactationanteriorpituitarystressmetabolicrategrowt
hreproductionlactationHypothalamicregulatorycenersOutput

hypothalamusreleasinghormoneshypothalamusinhibitinghormonesoxytocinADH
HKin
191
HKin 191
18
3) Endocrine organs
the posterior pituitary
does NOT synthesize hormones
storage and release center for oxytocin and ADH
Posterior
hypophyseal
veins
inferior
hypophyseal
artery
3)
Endocrine
organs
Hypothalamus:
signals to posterior
pituitary
Oxytocin:
neurocrine
hormone
HKin191stimuli:suckling,vaginaldilationresponse:myoepithelealcellcontractioninth
enipples,
uterinecontractions
3)
Endocrine
organs
Hypothalamus:
signals to posterior
pituitary
Antidiuretic
hormone
(ADH)
:
neurocrine
hormone
Synthesis
and
release
similar
to
oxytocin
stimuli:
stimulatory:
inhibitory:
response:
HKin
191
3)
Endocrine
organs
the anterior pituitary

synthesizes,
stores
and
releases
seven
hormones
hypothalamus
release
regulated
by
hypothalamic
hormones
HKin1914)lactrotrophs5)gonadotrophsanteriorpituitary
comprised
of
5
cell
types
1)
somatotrophs
2)
thyrotrophs
3)
corticotrophs
3)
Endocrine
organs
Hypothalamus:
signals to anterior
pituitary
target
cells
in
5
releasing
hormones
anterior
pituitary
1.
growth
hormone
releasing
hormone
(GHRH)
.
somatotrophs
2.
thyrotropin
releasing
hormone
(TRH)
.
thyrotrophs
3.
corticotrophin
releasing
hormone
(CRH)
.
corticotrophs
4.
gonadotrophic
releasing
hormone
(GnRH)
.
gonadotrophs
5.
prolactin
releasing
hormone
(LRH)
.
lactotrophs
2
inhibiting
hormones
HKin1911.growthhormoneinhibitinghormone(GHIH)somatotrophs2.prolactininhibitinghor
mone(LIH)lactrotrophs
Anterior pituitary blood flow (covered in lab)
plexusportalveins2oplexussuperiorhypophysealarterysuperiorhypophysealarteryprima
ryplexuscapillariesportalveinssecondaryplexuscaillariesanteriorhypophysealveinve
nouscirculation(toheart)
anteriorh.veinshypothalamicreleasing/inhibitinghormonesanterioraryanteriorpituit
aryhormones
HKin
191
Endocrine
physiology
Hypothalamus:
signals to anterior pituitary
1) Growth
hormone releasing hormone
(GHRH)
Growth
hormone inhibiting hormone
(GHIH)
HKin
191
somato=body
EndocrinephysiologyHypothalamus:signals to anterior pituitaryEndocrinephysiology
Hypothalamus:signals to anterior pituitary
pituitary tumours
can produce
excess hGH
start
in childhood
.
gigantism
start
in adults
.
acromegaly
HKin
191
Endocrine
physiology
Hypothalamus:
signals to anterior pituitary
2) Thyrotropin
releasing hormone (TRH)
T3
and
T4
act
systemically
to:
increase
basal
metabolic
rate
increase
fuel
usage
(decrease
storage)
accelerate
tissue
growth
stimulate
fat
consumption
HKin
191
Graves' disease
(hyperthyroidism)
autoimmune
disease
antibodies
attack
thyroid
cells
antibody
reaction
mimics
TSH
T3
and
T4
constantly
produced
symptoms:
weight
loss
nervousness
irritability
sweating
shakiness
rapid
pulse
HKin
191
Endocrine
physiology
Hypothalamus:
signals
to
anterior
pituitary
3)
corticotrophin
releasing
hormone
(CRH)
modulates
response
to
stress:
.
gluconeogenesis
and
lypolysis
(increase
fuel
availability)
inhibits
inflammation
and
immune
response
.
protein
catabolism
(e.g.
tyrosine
aminotransferase)
HKin
191
3)
Endocrine
organs:
Anterior
pituitary
summary
hypothalamus
anterior
pituitary
systemic
circulation
5releasinghormonesGHRHTRHCRHGnRHLRH2inhibitinghormonesGHIHLIH7hormones(from5cell
types)
HGH(humangrowthhormone)
TSH(thyroidstimulationhormone)
ACTH(adrenalcorticothropichormone)
LH(luteinisinghormone)
FSH(folliclestimulatinghormone)
MSH(melanocytestimulationhormone)
prolactin
HKin
191
3)
Endocrine
organs:
thyroid
gland
non-pituitary
mediated
hormones
Parafollicular
cells in
the thyroid
gland
_________
_
is
up-regulated
by
increased
plasma
Ca+
+
concentration
(release
is
not
triggered
by
TSH)
__________
_
inhibits
osteoclast
activity
.
decrease
release
of
calcium
from
bone
.
lowers
plasma
Ca+
+
concentration
HKin
191
3)
Endocrine
organs:
parathyroid
glands
Parathyroid glands:
tissue
nodules
on
lateral
surface
of
thyroid
gland
_____
_
is
up-regulated
by
decreased
plasma
Ca+
+
(release
is
not
triggered
by
TSH)
_____
_
stimulates
osteoclast
activity
.
increase
release
of
calcium
from
bone
______
_
stimulates
calcitriol
release
from
the
kidneys
.
increase
absorption
from
intestines
.
increases
plasma
Ca+
+
concentration
HKin
191
HKin 191
32
calcitriol
Ca++ dietary
input
Ca++ pool
Feces
Urine
PTH
calcitonin
Thyroid and parathyroid regulation of calcium
calcitriol
PTH
PTH stimulates
calcitriol release
3)
Endocrine
organs:
adrenal
glands
The
adrenal
cortex
adrenal cortex
anabolic
and
androgenic
activity
found
in
males
and
females
secondary
site
of
testosterone
synthesis
(primary
site:
testes)
growth
and
recovery
maintain
plasma
ion
homeostasis
HKin
191
Endocrine
physiology
The
adrenal
cortex
testosterone:
found
in
males
and
females
dihydrotestosterone (DHT) 30X more
potent
than testosterone
5a-reductase
found
in
prostrate,
testes
5a-reductase
androstenedione
DHEA
testosterone
dihydrotestosterone
HKin
191
5a
aaaa-reductase deficiency
male
pseudo-hermaphrodite
born with female
sexual organs
virilisation
may occur at
puberty
HKin
191
The
adrenal
cortex
testosteronestanozololnandroloneanabolicsteroids(forinterest,youarenotresponsibl
eforthesestructures)
LandisJohnsonChristie
HKin
191
Problems
with
roids
anabolic steroids: synthetic

versions of testosterone
reduces
activation
by liver (allowing ingestion)
increases anabolic
effects, decreases androgenic
effects
androgens
can be
converted to estradiol
(
a
potent
estrogen)
estradiol
promotes
breast development
(gynecomastia)
HKin191testosteroneestradiolaromatase
Endocrine
physiology
Problems
with
roids
psychological
effects (mood changes)
,
liver damage, acne, tendon weakness
testes
produce testosterone
testes size
and function maintained by FSH and LH
high levels
of testosterone suppress FSH
and LH
synthesis
therefore, testes shrink and sperm count drops
cause masculinisation in women
e.g.
breast
atrophy,
hirsutism,
deepening
of
voice
HKin
191
Androgen
receptors
androgens
bind
to
androgen
receptors
stimulate
virilization:
development
of
male
characteristics
other
hormones
produced
in
the
testes
suppresses
development
of
female
internal
reproductive
organs
(Mullarian
inhibitory
substance)
androgens
(especially
DHT)
+
MIS
.
male
HKin
191
Complete
androgen
insensitivity
syndrome
(CAIS)
(testicular
feminization)
anatomically women
incomplete reproductive organs
genetically male (XY)
will
fail
the
sex test
formerly used in the
Olympics
HKin
191
3)
Endocrine
organs:
the
adrenal
glands
The
adrenal
medulla
produces
catecholamines
(e.g.
epinephrine
and
norepinephrine)
the
stress
response
medulla
HKin
191
Endocrinephysiology
Catecholamines
20%
norepinephrine
80%
epinephrine
HKin
191
HKin 191
43
Catecholamine receptors
G protein-coupled, seven trans-membrane helix receptors
Signal transduction cascade
binding to receptor activates a G protein in the cell
activated G protein turns on adenylate cyclase
this increases cAMP
cAMP turns on protein kinases
kinases activate target proteins inside
outside
Catecholamines: mechanism of
action -stimulatory
activates
stimulatory
protein (Gs)
agonistbindsto
b-receptor

Ge.g.epinephrinenorepinephrinesalbutamol
Gs
activates
adenylate cyclase
increase
in cAMP
cAMP
activates
protein kinases
protein kinases
activate
target
Fig.
from
http://www.utdallas.edu/~tres/pharm
proteins
HKin
191
Endocrine
physiology
Catecholamines: mechanism of
action -inhibitory
activates
inhibitory
protein (Gi)
Gi
inhibits
adenylate cyclase
decrease
in cAMP
less
activation of
protein kinases
less
activation
agonistbindsto
a-receptor

e.g.epinephrinenorepinephrinesalbutamol
target
proteins
Fig.
from
http://www.utdallas.edu/~tres/pharm
HKin
191
Catecholamines:
mechanism
of
action
(epinephrine
vs.
norepinephrine)
1)
epinephrine
has
greater
effect
on
beta
receptors
increase
heart
rate
vasodilation
in
skeletal
muscle
(more
blood
to
muscle)
increased
Ouptake
(
.
respiration
and
pulmonary
blood
flow)
2
2)
norepinephrine
has
greater
effect
on
alpha
receptors
vasoconstriction
in
smooth
muscle
increase
blood
pressure
3)
epinephrine
has
much
greater
effect
on
metabolic
rate
e.g.
glycogenolysis
(release
of
glucose
for
use)
HKin
191
Stress:
the
fight
or
flight
response
1)
effector
organs
.
direct
neuro-modulation
of
target
organs
targeted
response
fast,
but
transient
2)
adrenal
medulla
(hormonal
stimulation)
.
hormonal
(catacholamine)
modulation
of
effector
organs
less
targeted
that
neural
stimulation
lasts
5
10
times
longer
than
neural
stimulation
HKin
191
Stress:
the
fight
or
flight
response
Inhibition digestivemotility waterrelease salivation localisedvasoconstriction

visceralbloodflow
cutaneousbloodflow
Stimulation
water
retention
localised
vasodilatation
.
pulmonary
blood
flow
.
cardiac
blood
flow
.
muscle
blood
flow
bronchial
dilation
and
respiration
cardiac
output
(HR
and
SV)
HKin
191
fast, transient responseslow,lasting responsecatecholaminescatecholamines
Stress:
the
fight
or
flight
response
hypothalamus
effectors
(e.g.
muscles)
s
ssy
yym
mmp
ppa
aat
tth
hhe
eet
tti
iic
ccn
nne
eer
rrv
vvo
oou
uus
sss
ssy
yys
sst
tte
eem
mmc
cci
iir
rrc
ccu
uul
lla
aat
tti
iio
oon
nn
HKin
191
Stress:
recovery
and
the
resistance
response
hypothalamus
triggered
hormonal
responses
purpose:
to
generate
energy
and
components
for
tissue
repair
response
involves:
cortisol
human
growth
hormone
(HGH)
triiodothyronine
(T3)
HKin
191
Stress:
recovery
and
the
resistance
response
1)
CRH
.
ACTH
.
release
cortisol
limits
inflammation
(improves
blood
flow
to
damaged
tissue)
increases
gluconeogenesis
(synthesis
of
glucose
from
pyruvate)
increase
lipolysis
(break
down
of
lipids
to
fatty
acids
for
use
as
fuel)
break
down
of
proteins
for
amino
acids
(for
repair)
HKin
191
Stress:
recovery
and
the
resistance
response
2)
GHRH
.
Human
Growth
Hormone
increase
lipolysis:
break
down
of
lipids
for
use
as
fuel
glycogenolysis:
breakdown
of
glycogen
in
liver
for
glucose
HKin
191
Stress:
recovery
and
the
resistance
response
3)
TRH
.
TSH
.
T3
stimulates
fuel
use
and
ATP
production
stimulates
tissue
growth
HKin
191
Stress:
recovery
and
the
resistance
response
complex,
integrated
neural:
hormonal
response
fight
flight
rest
repair
replace
rebuild
refuel
HKin
191
HKin191hypothalamussympatheticnervoussystemsympatheticnervoussystemcirculationci
rculationfast, transient responseslow,lasting responsecatecholaminescatecholamin
escortisolhGHGHRHTRHCRHACTHT3effectors(e.g.muscles)
3)
Endocrine
organs:
pancreas
endocrine
cells (islets
of Langerhans)
primary function: regulation of
blood sugar
trigger: high
blood glucose
beta
(b
)
cells
secrete
_________
_
Note:
the
pancreas
is
also
an
major
exocrine
gland
HKin
191
3)
Endocrine
organs:
pancreas
Type
I
Diabetes
mellitus
(insulin
dependent diabetes)
lack of
beta
cells
.
low/no insulin
failure to store glucose
blood glucose rises above healthy levels
buildup of glucose in urine
treat
with insulin
HKin
191
3)
Endocrine
organs:
pancreas
Type
II
Diabetes
mellitus
(insulin
resistant diabetes)
lack of insulin receptors

insulin produced
but not functional
similar symptoms to type I
treat
with diet
and lifestyle
changes
HKin
191
3)
Endocrine
organs:
pancreas
endocrine
cells (islets
of Langerhans)
primary function: regulation of
blood sugar
trigger: low
blood glucose
a
cells
secrete
_____________
_
stimulates
synthesis
of
glucose
in
liver
(gluconeogenesis)
releases
glucose
for
utilization
(glycogenolysis)
(i.
e
breakdown
of
glycogen
to
glucose)
HKin
191
HKin 191
60
3) Endocrine organs: the kidneys
Calcitriol (active form of vitamin D):
stimulates ____________________
Erythropoietin (Epo):
synthesized in response to tissue hypoxia
stimulates ______________________
increases ________________________
Ca++
HKin 191
Endocrinephysiology61HKin191Endocrinephysiology61
Endocrine
physiology
Great
moments
in
EPO
doping
1998 Tour de France ( Tour de
Dopage
)
400 vials of EPO

found in Festina team
car
entire team
kicked out
of race
HKin
191
Endocrine
physiology
Other organs
with endocrine functions
heart
-atrial natriuretic
factor (covered in cardio section)
muscle
bones
-insulin-like growth factors (NOT
covered in HKin191)
liver
stomach
gastrin
(covered in GI section)
intestines
-secretin and CCK (covered in GI section)
adipocytes
leptin
(covered in GI section)
reproductive organs
(NOT
covered in HKin191)
HKin
191
Endocrine
physiology
Summary
and
goals
of
the
endocrine
physiology
section
1)
describe
similarities/differences
between
neural
and
endocrine
systems
2)
describe
the
four
types
of
hormones
and
give
an
example
of
each
type
3)
differentiate
between
fat-and
water-soluble
proteins
including
transport
and
mechanism
of
control
on
target
cells
4)
describe
the
endocrine
functions
of
the
following
organs:
hypothalamus
kidney
anterior
and
posterior
pituitary
adrenal
glands
pancreas
5)
describe
the
role
of
the
hypothalamus
as
the
master
control
center
6)
describe
the
fight/flight
and
the
recovery/resistance
responses
HKin
191
Endocrinephysiology65Summary and goals of the endocrine physiology sectionEndocr
inephysiology65Summary and goals of the endocrine physiology section
7)
describe
the
pituitary
gland
including
structure
and
blood
flow
8)
describe
Graves
disease
and
explain
the
symptoms
9)
explain,
using
epinephrine
as
an
example,
how
a
hormone
can
elicit
different
responses
in
different
tissues
10)
recognize
the
following
hormones
and
briefly
describe
their
function
and
where
they
are
synthesized:
ADH
human growth hormone
erythropoietin
T3 and T4 adrenocorticothropic
hormone
glucagon
calcitonin
parathyroid hormone
insulin
calcitriol
thyroid stimulating hormone androgens
glucocorticoids
norepinephrine
and epinephrine oxytocin
cortisol
insulin-like growth factors
the 5 hypothalamic releasing hormones and the two inhibiting

hormones
HKin
191

Endocrine

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Endocrine

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EndocrinephysiologyEndocrinephysiology

3) Endocrine organs (covered in course)

growth and development

e.g. antidiuretic hormone (ADH)

(specific DNA sequence)

the anterior pituitary

anabolic steroids: synthetic

Inhibition digestivemotility waterrelease salivation localisedvasoconstriction

lack of insulin receptors

400 vials of EPO

the 5 hypothalamic releasing hormones and the two inhibiting

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