Endocrine Regulation

CHAPTER
3
Cell Signaling and
Endocrine Regulation
PowerPoint® Lecture Slides prepared by

Stephen Gehnrich, Salisbury University
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Cellular Communication
 Everything an animal does involves communication

among cells
 Example: moving, digesting food
 Cell signaling – communication between cells
 Signaling cell sends a signal (usually a chemical)
 Target cell receives the signal and responds to it

Types of Cell Signaling
Figure 3.1
Types of Cell Signaling
 Direct
 Signaling cell and target cell connected by gap
junctions
 Signal passed directly from one cell to another
 Indirect
 Signaling cell releases chemical messenger
 Chemical messenger carried in extracellular fluid
 Some may be secreted into environment
 Chemical messenger binds to a receptor on target cell
 Activation of signal transduction pathway
 Response in target cell

Indirect Signaling Over Short Distance
 Short distance
 Autocrine
 Chemical message diffuses back to signaling cell to
influence its activity
 Secreted by cells in a local area
 Ex. Eicosanoids ( prostaglandins, leukotrienes,
thromboxanes)
 Paracrine
 Chemical messenger diffuses to extracellular fluid and
nearby cell
 Has a localized effect on other tissues
 Ex. Eicosanoids, histamine

Indirect Signaling Over Long Distance
Long distances
 Endocrine System
 Chemical messenger (hormone) transported by
circulatory system
 Nervous System
 Electrical signal travels along a neuron and chemical
messenger (neurotransmitter) is released into the
synaptic cleft
 Influence postsynaptic cells

Direct Signaling
Gap junctions
 Specialized protein complexes (
connexins or innexins) create an
aqueous pore between adjacent
cells
 Movement of selected ions between
cells
 Changes in membrane potential
 Chemical messengers can travel
through the gap junction
 Example: cAMP
 Opening and closing of gap
junction can be regulated
 Close: intracellular Ca2+ ; intra
pH
Indirect Signaling
 Three steps
 Release of chemical messenger from signaling cell
(gland)
 Transport of messenger through extracellular
environment to target cell
 Communication of signal to target cell
 Systems for indirect signaling have similarities and
differences

Glands
Figure 3.3
Chemical Messengers
 Six classes of chemical messengers

 Peptides
 Steroids
 Amines
 Lipids
 Purines
 Gases
 Structure of chemical messenger (especially
hydrophilic vs. hydrophobic) affects signaling
mechanism

Indirect Signaling
Table 3.2
Peptide/Protein Hormones
 2-200 amino acids long  Hydrophilic
 Synthesized on the rough  Soluble in aqueous
ER solutions
 Travel to target cell
 Often as larger
dissolved in extracellular
preprohormones fluid
 Stored in vesicles  Bind to transmembrane
 Prohormones receptors
 Cut prohormone into  Signal transduction
active hormone in  Rapid effects on target cell
secretory vesicles  Half-life: short half-life
 Secreted by exocytosis from few sec. to few hours

Synthesis & Secretion of Peptide Hormones
Figure 3.4
Synthesis & Secretion of AVP
Figure 3.5
Transmembrane Receptor
Figure 3.6
Steroid Hormones
 Derived from cholesterol

 Synthesized by smooth ER or mitochondria
 Three classes of steroid hormones
 Mineralocorticoids ( aldosterone)
 regulate Na+ uptake by kidneys
 Electrolyte balance
 Glucocorticoides
 Stress hormones
 Reproductive hormones
 Regulate sex-specific characteristics

Steroid Hormones
 Hydrophobic

Can diffuse through plasma membrane

Cannot be stored in the cell

Must be synthesized on demand

Transported to target cell by carrier proteins
 Example: albumin; sex hormone-binding globulin
 High concentration of carrier proteins reduce the amount
of unbound hormone in the blood, reduce effective
concentration of the hormone
 Bind to intracellular or transmembrane receptors
 Slow effects on target cell (gene transcription)
 Stress hormone cortisol ( transmembrane receptor) has rapid
non-genomic effects

Steroid Hormones
Figure 3.8
Amine Hormones
 Chemicals that possess amine group (–NH2)

 Example: acetylcholine, catecholamines (dopamine,
norepinephrine, epinephrine), serotonin, melatonin,
histamine, thyroid hormones
 Sometimes called biogenic amines
 Some true hormones, some neurotransmitters, some
both
 Most hydrophilic
 Thyroid hormones are hydrophobic
 Diverse effects

Other Chemical Messengers
 Eicosanoids
 Most act as neurotransmitters,
paracrines
 Hydrophobic
 Transmembrane receptors
 Short half-life in extracellular
fluid
 Often involved in
inflammation and pain
 Example: prostaglandins,
leukotrienes
Figure 3.10
Other Chemical Messengers
 Gases
 Most act as paracrines
 nitric oxide (NO), carbon monoxide , hydrogen sulfide
 Nitric oxide: vasodilator: activates intracellular guanylate
cyclase to produce cGMP; PDE terminate NO signal
 Hydrogen sulfide: from cysteine; vasodilator to regulate
blood pressure by altering the structure and function of
K+ channels
 CO: vasodilator (blood vessels of the heart);
neurotransmitter ( hypothalamo-pituitary axis)
 Purines
 Function as neuromodulators and paracrines
 Bind to purinergic receptors ( transmembrane receptors)
 Example: adenosine, AMP, ATP, GTP
Communication to the Target Cell
 Receptors on target cell

 Hydrophilic messengers bind to transmembrane
receptor
 Hydrophobic messengers bind to intracellular
receptors
 Ligand
 Chemical messenger that can bind to a specific
receptor
 Receptor changes shape when ligand binds

Ligand-Receptor Interactions
 Ligand-receptor interactions are
specific
 Only the correctly shaped
ligand (natural ligand) can
bind to the receptor
 Ligand mimics
 Agonists – activate receptors
 Antagonists – block receptors
 Many ligand mimics act as
drugs or poisons

Ligand-Receptor Interactions
 A ligand may bind to more than one type of

receptor
 Receptor isoforms ( similar ligand binding domains
but differ in functional domains: different effects)
 Expressed on different target cells
 Different responses to the same ligand
 A single cell may have receptors for many different
ligands

Ligand-Receptor Binding
 L + R  L-R
 Formation of L-R
complex causes
response
 More free ligand (L)
or receptors (R) will
increase the response
 Law of mass action
 Receptors can become
saturated at high L
 Response is maximal

Changes in Number of Receptors
 Number of receptors affects number of
L-R complexes, change in the
responsiveness of the target cell
 More receptors   L-R complexes
  response
 Target cells can alter receptor number
 Down-regulation ( habitual drug
users)
 Target cell decreases the number
of receptors ( reduce sensitivity)
 Often due to high concentration
ligand
 Up-regulation ( adenosine vs.
caffeine)
 Target cell increases the number
of receptors
Ligand-Receptor Dynamics
 Affinity of receptor for ligand

affects number of
L-R complexes
 Higher affinity constant
(Ka)   response
 Higher affinity: Low
dissociation constant ( Kd);
saturate at lower ligand
concentration
Figure 3.13b
Inactivation of Ligand-Receptor Complex
 L-R complex must be inactivated to allow
responses to changing conditions
Figure 3.14
Signal Transduction Pathways
 Convert the change in receptor shape
to an intracellular response
 Four components
 Receiver
 Ligand binding region of
receptor
 Transducer
 Conformational change of the
receptor
 Amplifier
 Increase number of molecules
affected by signal
 Responder
 Molecular functions that
change in response to signal
Types of Receptors
 Intracellular
 Bind to hydrophobic
ligands
 Ligand-gated ion channels
 Lead to changes in
membrane potential
 Receptor-enzymes
 Lead to changes in
intracellular enzyme
activity
 G-protein-coupled
 Activation of membrane-
bound G-proteins
 Lead to changes in cell
activities
Intracellular Receptors
 Lipid-soluble ligand (
thyroid, steroid) diffuses
across cell membrane
 Binds to receptor in
cytoplasm or nucleus
 L-R complex binds to
specific DNA sequences (
response elements)
 Regulates the
transcription of target
genes
 increases or decreases
production of specific
mRNA

Changes in Gene Transcription
Figure 3.18
Ligand-Gated Ion Channels
 Ligand binds to
transmembrane receptor
 Receptor changes shape
opening a channel
 Ions diffuse across
membrane
 Ions move “down” their
electrochemical gradient
 Movement of ions
changes membrane
potential

Receptor Enzymes
 Ligand binds to
transmembrane
receptor
 Catalytic domain of
receptor starts a
phosphorylation
cascade
 Phosphorylation of
specific intracellular
proteins
 Receptor guanylate
cyclase: atrial
natriuretic peptides
(ANPs)
Receptor Tyrosine Kinases
• Insulin, epidermal
growth factor,
vascular
endothelial growth
factor
• Diabetes mellitus
is due to the defect
in the signal
transduction
pathway

• Transforming
growth factor
(TGF-β)

G-Protein-Coupled Receptors
 Ligand binds to transmembrane receptor

 Receptor interacts with intracellular G-proteins
 Named for their ability to bind guanosine nucleotides
 Subunits of G-protein dissociate
 Some subunits activate ion channels
 Changes in membrane potential
 Changes in intracellular ion concentrations
 Some subunits activate amplifier enzymes
 Formation of second messengers

G-Protein-Coupled Receptors
Figure 3.25
Second Messengers
Table 3.3
Inositol-Phospholipid Signaling
Figure 3.26
Cyclic-AMP Signaling
Ex. Glucagon, Adrenocorticotropic Hormone ( ACTH) binds to
receptors in the cell membrane of adrenal cortex for synthesis and
release of glucocorticoid
Figure 3.27
Interaction Among Transduction Pathways
 Cells have receptors for different ligands

 Different ligands activate different transduction
pathways
 Response of the cell depends upon the complex
interaction of signaling pathways

Regulation of Cell Signaling
 Cell signaling is important for regulation of

physiological processes
 Components of biological control systems
 Sensor
 Detects the level of a regulated variable
 Sends signal to an integrating center
 Integrating center
 Evaluates input from sensor
 Sends signal to effector
 Effector
 Target tissue that responds to signal from integrating
center
Regulation of Cell Signaling
 Set Point
 The value of the variable that the body is trying to
maintain
 Feedback loops
 Positive
 Output of effector amplifies variable away from the set
point
 Positive feedback loops are not common in physiological
systems
 Negative
 Output of effector brings variable back to the set point

Feedback Regulation

Pituitary Hormones
 Pituitary gland
secretes many
hormones
 Two distinct
anatomic sections:
 Anterior pituitary
(adenohypophysis)
 Posterior pituitary
(neurohypophysis)

Posterior Pituitary
 Extension of the hypothalamus
 Neurons that originate in
hypothalamus terminate in
posterior pituitary
 Neurohormones oxytocin
and vasopressin
synthesized in cell body
and travel in vesicles down
axons ( axonal transport)
 First-order endocrine pathway
 Hypothalamus receives
sensory input
 Hypothalamus serves as
integrating center

Anterior Pituitary
Hypothalamus synthesizes and

secretes neurohormones

Hypothalamic-pituitary portal
system

Anterior pituitary releases
hormones
 Tropic hormones
 Cause release of
another hormone
 Third-order endocrine
pathway

Hypothalamus and Anterior Pituitary
Figure 3.31
Regulation of Blood Glucose
 Precisely controlled  Insulin and glucagon are
 Blood glucose too low, secreted by pancreas
brain cannot function
 Direct feedback loops
 Blood glucose too high,
 Pancreas also receives
osmotic balance of blood
neural and hormonal
disturbed
signals
 Hormones
 Antagonistic pairing
 Insulin ( pancreatic beta
cells) lowers blood glucose  Hormones that have
levels opposing effects
 Glucagon (pancreatic
alpha cells) raises blood
glucose levels

Pathways Regulating Insulin Secretion
Figure 3.33
Antagonistic Regulation
Figure 3.34
Additivity and Synergism
Figure 3.35
Additivity and Synergism
 Additivity
 When hormones cause same response in a target cell
 Hormones do not use the same signaling pathway
 Example: glucagon, epinephrine, and cortisol all raise
blood glucose by different mechanisms
 Response of target cell to combinations of these hormones is
additive
 Synergism
 When hormones enhance effect of other hormones
 Response of target cell to combinations of these hormones
more than additive
 Permissive Effect
 Complete effects of one hormone are dependent on the
presence of another hormone

Hormones of the Adrenal Cortex

Endocrine Pathologies
 Cushing’s Syndrome vs. Addison’s Disease
 Diabetes insipidus: Hyposecretion of
antidiuretic hormone (ADH) or vasopressin
Excessive urine output; Loss of
electrolytes
Alcohol inhibits ADH secretion
Dwarfism (midgetism) vs. Gigantism;
Acromegaly ( hypersecretion of after long bone
growth)
Goiter, Hypothyroidism (cretinism,
myxedema) vs. Hyperthyroidism ( Graves’
disease)
Hyperparathyroidism leads to
osteoporosis

Roles of the Hypothalamus and Adrenal
Glands in the Stress Response

Vertebrate Stress Response
 Interaction between nervous and endocrine systems

 Sense organs detect “stress”
 Activation of sympathetic nerves
 Increased heart rate, respiration, dilation of airways
 Decreased secretion of insulin from pancreas
 Increased secretion of glucagon from pancreas
 Increased secretion of epinephrine from adrenal medulla
 Increase in blood glucose level

Hypothalamic-pituitary axis stimulates the
adrenal cortex
 Hypothalamus
 Secretes corticotropin-releasing
hormone (CRH)
 Anterior pituitary
 Secretes adrenocorticotropic
hormone (ACTH)
 Adrenal cortex
 ACTH binds to G protein-
coupled receptor via cAMP to
secrete cortisol ( glucocorticoid)
 Glucocorticoid binds to
intracellular receptor; hormone-
receptor complex regulates
transcription
Figure 3.37
Control of Glucose and lactate Levels in Arthropods
 Crustacean hyperglycemic
hormone (CHH)
 Neurohormone from crab
eyestalk
 Negative feedback: Secreted
in response to low glucose in
blood/hemolymph
 CHH acts via cGMP pathway
 Positive feedback: CHH
binds to target cells produce
lactate and release to
circulation which causes the
cells to release more CHH
Figure 3.36
Adrenal Tissue in Different Vertebrates
Figure 3.38
Evolution of Cell Signaling
 Endocrine systems of animals diverse

 Suggests multiple evolutionary origins
 Chemical messengers, receptors, and cell signaling
mechanisms of animals share many similarities
 Suggests a common ancestor

Vertebrate Hormones
 Evolutionary changes in way tissues respond to a

hormone, rather than a change in hormone
molecules
 Some hormones have same effect in different
animals
 Example: human growth hormone increase growth
rate in fish; estrogen from pregnant mares can be used
in post-menopausal women
 Some hormones have a different effect in different
animals
 Example: prolactin stimulates milk production in
mammals, inhibits metamorphosis and promotes
growth in amphibians, regulates water balance in fish

Endocrine Regulation

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CHAPTER

PowerPoint® Lecture Slides prepared by

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

 Everything an animal does involves communication

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

 Six classes of chemical messengers

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

 Derived from cholesterol

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

 Chemicals that possess amine group (–NH2)

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

 Receptors on target cell

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

 A ligand may bind to more than one type of

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

 Affinity of receptor for ligand

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Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

 Ligand binds to transmembrane receptor

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 Cells have receptors for different ligands

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

 Cell signaling is important for regulation of

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Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Hypothalamus synthesizes and

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Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

 Interaction between nervous and endocrine systems

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

 Endocrine systems of animals diverse

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

 Evolutionary changes in way tissues respond to a

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