Download Lect 08 Endocrine 1 - intro (KKD)

Endocrine System
Lect # 1
Introduction
Prof Kumlesh K. Dev
Department of Physiology
Chapter 4 Principles of Neural and Hormonal Communication
Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning
Some learning outcomes
• principles
• types of chemical signals
• receptors types
• feedback
eedbac regulation
egu at o
• major hormones
• pituitary
• hypothalamic
• adrenal
• hypothalamo-pituitary axis
• hormonal regulation of
• growth
• glucose and metabolic
• calcium
Types of cellular communication
Classification
communication
i ti iis critical
iti l ffor cellll
– survival
– function
two major communication systems:
– nervous system
– endocrine system
Chapter 4 Principles of Neural and Hormonal Communication
Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning
Four types of chemical messengers
Classification
1)) Autocrine/Paracrine
• local chemical messengers
• exert effect on neighbouring cells (paracrine)
or on same cell (autocrine)
2) Neurotransmitter
• short-range
h t
chemical
h i l messengers
• diffuse across narrow space (synapse) to act
on adjoining
dj i i ttargett cellll ((another
th neuron, a
muscle, or a gland)
Four types of chemical messengers
Classification
3)) Neurohormones
• hormones released into blood by
neurosecretory neurons
• distributed through blood to distant target cells
4) Hormones
• long-range
l
messengers
• secreted into blood by endocrine glands in
response to
t appropriate
i t signal
i
l and
d actt on
distant target cells
1. Autocrine/Paracrine
Classification
– chemical messenger
released from a cell :
Secretory Cell
autocrine
– can act on itself
(autocrine)
– can act on another cell
close by (paracrine)
close-by
paracrine
Cell #2
2. Neurotransmitters
Classification
– neurotransmitters
released from
synaptic
y p vesicles
– diffuse across
synapse between
b t
two
t
cells
synapse
with
muscles
l
– transmitter binds a
receptor
p
– receptor activation
stimulates
ti l t the
th cellll
synapse
with
another
neuron
synapse
with
glands
3. Neurohormones
Classification
– released from
synaptic vesicles
by neuron
– released into
blood
– acts in manner
similar to
hormones
4. Hormones
Classification
– messengers off
endocrine system
– released from
endocrine g
gland into
blood
– transported
t
t d in
i blood
bl d
– target cell expresses
specific receptors
Nervous and Endocrine Communication
Classification
Property
Nervous System
Endocrine System
Structure
Wired system of neurons Wireless system of glands
Chemical Messenger Neurotransmitter
Hormones
Target
g site
Veryy close
Far awayy
Distance of Action
Across synaptic cleft
Carried by blood
Speed of Response
milliseconds
mins to hours
Duration of Action
milliseconds
mins to days
Major Function
fast precise responses
long duration responses
Four Types of hormones
Classification
• Two hormone categories based on solubility
– Hydrophilic (lipophobic,
(lipophobic water soluble)
• 1. Peptide hormones
• 2.
2 Catecholamines
C t h l i
– Lipophilic (hydrophobic,
(hydrophobic water insoluble)
• 3. Thyroid hormone
• 4. Steroid hormones
Four Types of hormones
Classification
Property
Peptide
Catecholamine
Thyroid
Steriods
Structure
amino acids
tyrosine
derivative
iodinated
tyrosine
cholesterol
derivative
Solubility
hydrophilic
lipophobic
hydrophilic
lipophobic
lipophilic
hydrophobic
lipophilic
hydrophobic
Receptors
on cell surface
on cell surface
inside cell
inside cell
Synthesis
in ER
in cytosol
organelles
intracell
Storage
granules
granules
colloid
lipid droplets
Secretion
exocytosis
of granules
exocytosis
of granules
endocytosis
of colloid
diffusion
Blood
Transport
free hormone
plasma bound
plasma bound
plasma bound
Hormone
hypothalamic,
pituitary, pineal,
pancreas,
parathyroid, GIT,
kidney, liver, heart
adrenal medulla
thyroid
follicular
adrenal cortex
gonads, Vit D
Steroid hormone
Synthesis
ffemale
l sex
hormone
male sex
hormone
adrenal cortex
hormone
-
adrenal cortex
hormone
steroid hormones derived from cholesterol
are small lipid-soluble molecules
diff se thro
diffuse
throw cell membrane
receptor is intracellular
female sex
hormone
Steroid hormone
Synthesis
All steroid hormones are produced via cholesterol
2 Types of Receptors
Receptors
• surface receptors
– bind peptides & catecholamines
– at cell membrane
• nuclear receptors
– bind thyroid & steroid hormones
– inside the cell
Surface Receptors
Receptors
• allll cells
ll maybe
b exposed
d tto
hormones via circulation
peptides
p
p
& catecholamines
ion channel
• only
l cells
ll with
ith receptors
t
for hormone can respond
• extracellular chemical
(hormone) binds to
surface receptor
• receptor activation alters
– channel function
– second-messenger
systems
enzyme
change
g in
ion flow
(e.g. Na,
Ca, K, Cl)
Increased
product signal
(eg cAMP)
Nuclear Receptors
Receptors
• steroid receptors bind
steroid hormone
• hormone-receptor
hormone receptor complex
becomes a transcription
factor (alters gene
transcription))
• each steroid receptor binds
a unique
i
DNA sequence
(response element within
an enhancer region)
g )
• this alters the rate of
transcription
thyroid
y
& steroid hormones
plasma
protein
carrier
oestrogen
oestrogen receptor
protein
synthesis
mRNA
transcription
trans
loca
tion
Surface Receptor Structure
Receptors
• receptor domains
•
ligand binding domain (LBD)
•
7 transmembrane domains (TMDs)
•
G-protein coupled
• mechanism
•
•
LBD
TMDs
peptide hormone binds to receptors
on the surface of the cell
•
activates G-protein
•
induces intracellular signals
Neuropeptide Examples: Prolactin,
Adrenocorticotrophic hormone (ACTH),
Antidiuretic hormone (vasopressin),
Oxytocin, Insulin, Somatostatin
G-prot
PLC
AC
cAMP
IP3
DAG
PKA
Ca2+
PKC
Nuclear Receptor Structure
Receptors
• receptor domains
•
Hormone/Ligand binding domain (LBD)
•
DNA binding domain binds steroid
response element (SRE).
•
Nuclear Localization Signal (NLS)
covered by heat shock proteins (HSP)
LBD
NLS
e.g. glucocorticoid
receptor
HSP
SRE-BD
• mechanism
•
binding of hormone induces
detaches HSP; uncovers NLS
•
receptor+hormone enters nucleus
•
•
acts as a transcription factor
Examples:
E
l
E
Estrogen,
t
Glucocorticoid
Gl
ti id (Cortisol),
(C ti l)
Mineralocorticoid (Aldosterone), Progesterone,
Androgen (Testosterone)
transcription
SRE
nucleus
Receptor Regulation
Receptors
• target cell may be unresponsive due to lack of
receptors
t
(physiological,
( h i l i l genetic,
ti di
disease))
• one hormone can influence activity of another hormone
b regulation
by
l ti off it
its receptor:
t
Permissiveness
– one hormone is required for another hormone to work
Synergism
– actions of several hormones are complimentary
– combined effect is greater than sum of separate effects
Antagonism
– one hormone inhibits another hormone’s receptors
– reduces effectiveness of second hormone
Summary so far
Summary
 Four types of chemical signals
 1) A
Autocrine/Paracrine
t i /P
i
 2) Neurotransmitter
 3) Neurohormones
 4) Hormones
 Four
types of hormones
 1) Peptide hormones
 2) Catecholamines
 3) Thyroid hormone
 4) St
Steroid
id h
hormones
 Types
of receptors
 1) Extracellular
 2) Intracellular
?
The endocrine system
Endocrine System
Endocrine System
Overall functions
–
–
–
–
–
–
–
regulate organic metabolism
controls
t l water
t and
d electrolyte
l t l t b
balance
l
induces adaptive changes to cope with stress
promotes
t growth
th and
d development
d
l
t
controls reproduction
regulates red blood cell production
controls circulation, digestion, absorption of food
Endocrine Hormone Concentrations
Endocrine System
• plasma
l
conc. off hormones
h
controlled
t ll d b
by rate
t of:
f
– secretion
– metabolism and excretion
– binding to plasma proteins
• secretory output of endocrine cells controlled by
– neurall input
i
– other hormones
Neuro-Endocrine System
Endocrine System
 nervous and endocrine systems co-regulate
many physiological functions
 study of this is called Neuro-Endocrinology
 Neuro-Endocrinology studies how the brain
regulates
g
Pituitary
y hormone secretion
Neuro-Endocrine cells
Classification
Neuroendocrine cells release neurohormones
Found in, for example:
•
•
•
•
•
•
•
•
adrenal medulla
thyroid
islet of Langerhangs
pituitary
p
y cells
renin-secreting cells
gastro-intestinal tract
pancreas
lower respiratory tract
Primary & Secondary Endocrine Glands
Endocrine System
Primary
P
i
Endocrine
E d
i Organs
O
– discrete organs
– main function is endocrine hormone release
– pituitary, thyroid, parathyroid, adrenal and
pineal
i
l glands
l d
Secondary
S
d
Endocrine
E d
i Organs
O
– dispersed in organs
– have other major functions
– heart, kidney, liver, etc.
Endocrine Glands
Endocrine System
– derived from epithelial tissue
–
composed of clumps of
secretory cells
–
surrounded by capillaries
(fenestrated)
–
exocrine glands have ducts
– endocrine glands have no
duct system
Exocrine Glands: Classify by Morphology
Exocrine System
Simple Types
Endocrine glands
─ secret hormones into
bl d t
bloodstream
Exocrine glands
─ discharge products
via duct
tubular
large
intestine
acinar
urethra
branched
tubular
stomach
branched
acinar
Compound Types
Exocrine Types
─ simple / compound
tubular
acinar
coiled
tubular
sweat
glands
Exocrine Glands: Classify by Secretion
Exocrine System
Merocrine (eccrine) Secretion
• exocytosis
• most common type of secretion
Apocrine
p
Secretion
• membrane-bound vesicles
• example: breasts, sweat glands
Holocrine Secretion
• rupture off secretory cells
ll
• example: sebaceous glands
Feedback
Endocrine System
─ endocrine glands secretion
triggered by
─ hormones
─ neurotransmitters
─ metabolic factors
─ two types of feedback loops
─ long-loop
─ short-loop
─ feedback can be
─ excitatory
y
─ inhibitory
Feedback Mechanisms
Endocrine System
Gland 1
-
Positive Feedback
e.g. Hormone 3 activates
Gland 2
Hormone 1
Gland 2
Negative Feedback
Hormone 2
e.g.
g Hormone 3 inhibits
Gland 1
Gland 3
Hormone 3
+
Trophic Hormones
Endocrine System
• ttrophic
hi hormones
h
regulate
l t secretion
ti
other hormones (either releasing or
inhibitory)
• example
l
– thyroid-stimulating hormone (TSH)
– secreted from anterior pituitary
– stimulates thyroid hormone secretion from
thyroid gland
– maintains structural integrity of thyroid
gland
Anterior pituitary
Thyroid
stimulating
hormone (TSH)
Thyroid gland
Thyroid Hormone
(T3.T4)
Disease: Hyposecretion
Endocrine System
Primary hyposecretion
• due to abnormality within gland
• causes
–
–
–
–
–
–
–
genetic
dietary (eg lack of iodine)
chemical or toxic
immunologic (autoimmune diseases)
cancer
surgery (removal / Iatrogenic)
idiopathic (unknown)
Secondary hyposecretion
• deficiency of tropic hormone
Disease: Hypersecretion
Endocrine System
• Causes
– tumours continuously secrete hormone
– immune factors
• Primary hypersecretion
– too much hormone secreted due to
abnormality within gland
• Secondary hypersecretion
– excessive stimulation of g
gland causes
oversecretion
Summary
Summary
4 types of chemical signals
1) Autocrine/Paracrine
2) Neurotransmitter
3) Neurohormones
4) Hormones
4 types of hormones
1) Peptide hormones
2) Catecholamines
3) Thyroid hormone
4) Steroid hormones
2 Types of receptors
1) Extracellular
2)) Intracellular
Feedback and Tropic
hormones
1) Long and short loops
2) Positive and negative
2. Types of glands
1) Primary
2) Secondary
Causes and types of
1) h
hyposecretion
ti
2) hypersecretion