Lect E1 - Endocrine intro
Some learning outcomes
Endocrine System
Lect # 1
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Introduction
Prof Kumlesh K. Dev
D
Department
off Physiology
Ph i l
principles of feedback regulation
peripheral effects of pituitary hormones
how growth is regulated by hormones
why puberty initiates both growth and its cessation
effects of abnormal GH before and after puberty
common synthesis of adrenal & gonadal steriods
hypothalamo-pituitary axis function
major role of pineal gland in endocrine regulation
normal range of plasma free calcium conc
hormonal regulation of calcium balance
causes and consequences of hypocalcaemia
Chapter 4 Principles of Neural and Hormonal Communication
Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning
Types of cellular communication
Classification
Communication is critical for cell survival
2 major regulatory systems:
– Nervous System
– Endocrine System
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 chemical messengers
• Diffuse across narrow space (synapse) to act
on adjoining target cell (another neuron, a
muscle, or a gland)
Chapter 4 Principles of Neural and Hormonal Communication
Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning
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Lect E1 - Endocrine intro
Four types of chemical messengers
1. Autocrine/Paracrine
Classification
Classification
3) Neurohormones
• Hormones released into blood by
neurosecretory neurons
• Distributed through blood to distant target cells
– chemical messenger
released from a cell :
– can act on itself
(autocrine)
4) Hormones
• Long-range messengers
• Secreted into blood by endocrine glands in
response to appropriate signal and act on
distant target cells
– can act on another cell
close-by (paracrine)
2. Neurotransmitters
Cell #2
3. Neurohormones
Classification
Classification
– Neurotransmitters
released from
synaptic vesicles
– Released from
synaptic vesicles
by neuron
– Diffuse across
synapse between two
cells
synapse
with
muscles
– Transmitter binds a
receptor
– Receptor activation
stimulates the cell
Secretoryy Cell
synapse
with
another
neuron
synapse
with
glands
– Released into
blood
– Acts in manner
similar to hormones
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Lect E1 - Endocrine intro
4. Hormones
Nervous and Endocrine Systems
Classification
– Messengers of
endocrine system
– Released from
endocrine gland into
blood
– Transported in blood
– Target cell:expresses
specific receptors
Neuroendocrine cells
Classification
Property
Nervous System
Endocrine System
Structure
Wired system of neurons Wireless system of glands
Chemical Messenger Neurotransmitter
Hormones
Target site
Very close
Far away
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
Types of hormone
Classification
Neuroendocrine cells release neurohormones
and are found in, for example:
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adrenal medulla
thyroid
islet of Langerhangs
pituitary cells
renin-secreting cells
gastro-intestinal tract
pancreas
lower respiratory tract
Classification
• Two hormone categories based on solubility
– Hydrophilic (lipophobic, water soluble)
• Peptide hormones
• Catecholamines
– Lipophilic (hydrophobic, water insoluble)
• Thyroid hormone
• Steroid hormones
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Lect E1 - Endocrine intro
Types of hormone: characteristics
Steroid hormone
Classification
Property
Peptide
Catecholamines
Thyroid
Steriods
Structure
amino acids
tyrosine
derivative
iodinated
y
tyrosine
cholesterol
derivative
Solubility
hydrophilic
lipophobic
hydrophilic
lipophobic
lipophilic
hydrophobic
lipophilic
hydrophobic
Synthesis
in ER
in cytosol
organelles
intracell
Storage
granules
granules
colloid
lipd droplets
Secretion
exocytosis
of granules
exocytosis
of granules
endocytosis
of colloid
diffusion
Blood
Transport
free hormone
plasma bound
plasma bound
plasma bound
Receptors
on cell surface
on cell surface
inside cell
inside cell
Hormone
hypothalamic,
pituitary, pineal,
pancreas,
parathyroid, GIT,
kidney, liver, heart
adrenal medulla
thyroid
follicular
adrenal cortex
gonads, Vit D
Steroid hormone
Synthesis
female sex
hormone
male sex
hormone
adrenal cortex
hormone
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adrenal cortex
hormone
female sex
hormone
steroid hormones derived from cholesterol
are small lipid-soluble molecules
diffuse throw cell membrane
receptor is intracellular
Surface Receptors
Synthesis
Receptors
• all cells maybe exposed to
hormones via circulation
peptides & catecholamines
ion channel
• only cells with receptors
for hormone can respond
• extracellular chemical
(hormone) binds to
surface receptor
• receptor activation alters
– channel function
– second-messenger
systems
enzyme
change in
ion flow
(e.g. Na,
Ca, K, Cl)
Increased
product signal
(eg cAMP)
All steroid hormones are produced via cholesterol modification
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Lect E1 - Endocrine intro
Nuclear Receptors
Surface Receptor Structure
Receptors
• steroid receptors bind
steroid hormone
Receptors
thyroid & steroid hormones
• Receptor Domains
•
plasma
protein
carrier
• hormone-receptor complex
becomes a transcription
factor (alters gene
transcription)
• each steroid receptor binds
a unique DNA sequence
(response element within
an enhancer region)
oestrogen receptor
oestrogen
protein
synthesis
ligand binding domain (LBD)
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7 transmembrane domains (TMDs)
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G-protein coupled
LBD
• Mechanism
mRNA
transcription
trans
locati
on
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peptide hormone binds to receptors on
the surface of the cell
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activates G-protein
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induces intracellular signals
TMDs
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Nuclear Receptor Structure
Neuropeptide Examples: Prolactin,
Adrenocorticotrophic hormone (ACTH),
Antidiuretic hormone (vasopressin),
Oxytocin, Insulin, Somatostatin
• Receptor Domains
•
DNA bi
binding
di d
domain
i bi
binds
d steroid
t id
response element (SRE).
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Nuclear Localization Signal (NLS)
covered by heat shock proteins (HSP)
LBD
NLS
• Mechanism
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receptor+hormone enters nucleus
•
acts as a transcription factor
HSP
SRE-BD
binding of hormone induces detachment
of HSP; uncovers NLS
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e.g. glucocorticoid
receptor
p
transcription
SRE
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Examples: Estrogen, Glucocorticoid
(Cortisol), Mineralocorticoid (Aldosterone),
Progesterone, Androgen (Testosterone)
cAMP
IP3
DAG
PKA
Ca2+
PKC
Steroid hormone receptors
Receptors
Hormone/Ligand binding domain (LBD)
PLC
AC
• this alters the rate of
transcription
•
G-prot
Receptors
• Type I receptors
– Sex hormone receptors
• Androgen receptor
• Estrogen receptor
• Progesterone receptor
– Glucocorticoid receptor
– Mineralocorticoid receptor
• Type II receptors (No HSP association)
– Vitamin A receptor (vitamin A)
– Vitamin D receptor (vitamin D)
– Retinoid receptor
– Thyroid hormone receptor
nucleus
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Lect E1 - Endocrine intro
Receptor Regulation
Summary so far
Receptors
• target cell may be unresponsive due to lack of
receptors (physiological, genetic, disease)
• one hormone
h
can iinfluence
fl
activity
ti it off another
th h
hormone
by regulation of its receptor:
Permissiveness
Summary
9 Four types of chemical signals
9 1) Autocrine/Paracrine
9 2) Neurotransmitter
9 3) N
Neurohormones
h
9 4) Hormones
9 Four types of hormones
– one hormone is required for another hormone to work
Synergism
– actions of several hormones are complimentary
p
y
– combined effect is greater than sum of separate effects
Antagonism
– one hormone inhibits another hormone’s receptors
– reduces effectiveness of second hormone
Primary & Secondary Endocrine Glands
9 1) Peptide hormones
9 2) Catecholamines
9 3) Thyroid hormone
9 4) Steroid hormones
9 Types of receptors
9 1) Extracellular
9 2) Intracellular
? Types of glands
Endocrine System
Endocrine System
– endocrine glands are derived from
epithelial tissue
–
these glands are composed of
clumps of secretory cells
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surrounded by capillaries
(fenestrated)
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unlike exocrine glands, endocrine
glands have no duct system
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endocrine glands may exist in
Primary Endocrine Organs
(discrete organs - pituitary, thyroid,
parathyroid, adrenal and pineal glands)
Endocrine System
Overall functions
– regulate organic metabolism
– controls water and electrolyte balance
– induces adaptive changes to help cope with
stress
– promotes growth and development
– controls reproduction
– regulates red blood cell production
– controls circulation, digestion, absorption of food
Secondary Endocrine Organs
(dispersed in organs with other major
functions – heart, kidney, liver, etc..)
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Lect E1 - Endocrine intro
Neuroendocrine System
Hormone Signalling
Endocrine System
¾ many
a yp
physiological
ys o og ca functions
u ct o s a
are
e co
co-regulated
egu ated
by the nervous system and the endocrine
system
¾ study of this relationship is the focus of
neuroendocrinology
¾ neuroendocrinology primarily concerns the way
the brain regulates pituitary hormone
secretion
Hormone Concentrations
Endocrine System
hormones secreted by endocrine gland cells
• enter blood and distributed throughout
g
body
y
• can act at distant target sites
hormone secretion by endocrine glands triggered by
many signals:
• insulin secretion regulated by blood glucose conc
• secretion of sex hormones from ovaries and
testes controlled by anterior pituitary hormones
• oxytocin secretion from posterior pituitary regulated
by neurotransmitter release
Endocrine Dysfunction: Hyposecretion
Endocrine System
• plasma conc. of hormones is controlled by rate of
secretion
• secretory output of endocrine cells controlled by
– neural input
– another hormone
• plasma
p
conc. also influenced by
y
– rate of removal from blood by metabolism and
excretion
– rate of activation or its extent of binding to
plasma proteins
Endocrine System
Primary hyposecretion
• due to abnormality within gland
• causes
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genetic
dietary (eg lack of iodine)
chemical or toxic
immunologic (autoimmune diseases)
cancer
Iatrogenic (eg surgical removal)
idiopathic (unknown)
Secondary hyposecretion
• deficiency of tropic hormone
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Lect E1 - Endocrine intro
Endocrine Dysfunction: Hypersecretion
Feedback
Endocrine System
Endocrine System
• Causes
– Tumours continuously secrete hormone
– Immune factors
─ hormone production is regulated
by status of tissue which is
under hormonal control
• Primary hypersecretion
– too much hormone secreted due to
abnormality within gland
─ in pituitary and hypothalamus,
target tissues communicate
hormonally, neurally, or via
metabolic factors
─ two types
yp of feedback loops
p are
long-loop and short-loop
feedback
• Secondary hypersecretion
– excessive stimulation of gland causes
oversecretion
─ adrenal cortex provides
examples of both
Control by Feedback Mechanisms
Tropic Hormones
Endocrine System
Gland 1
-
Positive Feedback
e.g. Hormone 3 activates
Gland 2
Hormone 1
Gland 2
Negative
g
Feedback
Hormone 2
e.g. Hormone 3 inhibits
Gland 1
Gland 3
Hormone 3
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Endocrine System
• hormones regulating secretion other
hormones are called releasing factors
or inhibitory factors and classified as
trophic hormones
• these can stimulate/maintain endocrine
target tissues
• example
– 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)
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Lect E1 - Endocrine intro
Exocrine Glands: Classify by Morphology
Exocrine System
Exocrine Glands: Classify by Secretion
Exocrine System
Simple Types
Merocrine (eccrine) Secretion
• exocytosis
y
• most common type of secretion
Endocrine glands
─ secret hormones into
bloodstream
Exocrine glands
─ discharge products
via duct
tubular
large
intestine
acinar
urethra
branched
tubular
stomach
branched coiled
tubular
acinar
sweat
glands
Apocrine Secretion
• membrane-bound vesicles
• example: breasts, sweat glands
Compound Types
Exocrine Types
─ simple / compound
Holocrine Secretion
• rupture of secretory cells
• example: sebaceous glands
tubular
acinar
Summary
Summary
Four types of chemical signals
1) Autocrine/Paracrine
2) Neurotransmitter
3) Neurohormones
4) Hormones
Four types of hormones
1) Peptide hormones
2) Catecholamines
3) Thyroid hormone
4) Steroid hormones
Types of receptors
1) Extracellular
2) Intracellular
Feedback and Tropic
hormones
1) Long and short loops
2) Positive and negative
Types of glands
1) Primary
2) Secondary
Causes and types of
1) hyposecretion
2) hypersecretion
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