Chapter 4

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
 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
 Paracrine
 Chemical messenger diffuses to nearby cell
 Autocrine
 Chemical message diffuses back to signaling cell

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

Types of Cell Signaling
Figure 3.1
Direct Signaling
 Gap junctions
 Specialized protein complexes create an aqueous pore
between adjacent cells
 Movement of 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

Gap Junction
Figure 3.2
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
Indirect Signaling
Table 3.1
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

 Synthesized on the rough ER
 Often as larger preprohormones
 Stored in vesicles
 Prohormones
 Secreted by exocytosis

Peptide/Protein Hormones
 Hydrophilic
 Soluble in aqueous solutions
 Travel to target cell dissolved in extracellular fluid
 Bind to transmembrane receptors
 Signal transduction
 Rapid effects on target cell

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
 Electrolyte balance
 Glucocorticoides
 Stress hormones
 Reproductive hormones
 Regulate sex-specific characteristics

Synthesis of Steroid Hormones
Figure 3.7
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
 Bind to intracellular or transmembrane receptors
 Slow effects on target cell (gene transcription)
 Stress hormone cortisol 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 paracrines
 Hydrophobic
 Often involved in
inflammation and
pain
 Example:
prostaglandins,
leukotrienes
Figure 3.10
Other Chemical Messengers
 Gases
 Most act as paracrines
 Example: nitric oxide (NO), carbon monoxide
 Purines
 Function as neuromodulators and paracrines
 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

Figure 3.11
 A ligand may bind to more than one type of

receptor
 Receptor isoforms
 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

Ligand-Receptor Binding
Figure 3.12
Changes in Number of Receptors
 Number of receptors affects number of L-R

complexes
 More receptors   L-R complexes   response
 Target cells can alter receptor number
 Down-regulation
 Target cell decreases the number of receptors
 Often due to high concentration ligand
 Up-regulation
 Target cell increases the number of receptors

Changes in Number of Receptors
Figure 3.13a
Ligand-Receptor Dynamics
 Affinity of receptor
for ligand affects
number of
L-R complexes
 Higher affinity
constant (Ka)  
response
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

Transduction Pathway
Figure 3.15
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

Types of Receptors
Figure 3.16
Intracellular Receptors
 Ligand diffuses across cell membrane

 Binds to receptor in cytoplasm or nucleus
 L-R complex binds to specific DNA sequences
 Regulates the transcription of target genes
 increases or decreases production of specific mRNA

Intracellular Receptors
Figure 3.17
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

Ligand-Gated Ion Channels
Figure 3.19
Receptor Enzymes

 Catalytic domain of receptor starts a
phosphorylation cascade
 Phosphorylation of specific intracellular proteins

Receptor Enzymes
Figure 3.20
G-Protein-Coupled Receptors

 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
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
Figure 3.28
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
 First-order endocrine pathway
 Hypothalamus receives sensory input
 Hypothalamus serves as integrating center

Posterior Pituitary
Figure 3.29
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

Anterior Pituitary
Figure 3.30
Hypothalamus and Anterior Pituitary
Figure 3.31
Regulation of Blood Glucose
 Precisely controlled
 Blood glucose too low, brain cannot function
 Blood glucose too high, osmotic balance of blood
disturbed
 Hormones
 Insulin lowers blood glucose levels
 Glucagon raises blood glucose levels

Regulation of Blood Glucose
 Insulin and glucagon are secreted by pancreas

 Direct feedback loops
 Pancreas also receives neural and hormonal signals
 Antagonistic pairing
 Hormones that have opposing effects

Pathways Regulating Insulin Secretion
Figure 3.33
Antagonistic Regulation of Blood Glucose
Figure 3.34
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

Additivity and Synergism
Figure 3.35
Control of Glucose Levels in Arthropods
 Crustacean
hyperglycemic
hormone (CHH)
 Neurohormone from
crab eyestalk
 Secreted in response
to low glucose in
blood/hemolymph
Figure 3.36
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
 Secretes cortisol
 Stimulates target cells to increase blood glucose level

Figure 3.37
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 affect 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 affect in different
animals
 Example: prolactin stimulates milk production in
mammals, inhibits metamorphosis and promotes
growth in amphibians, regulates water balance in fish
Vertebrate Hormones
Table 3.3

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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

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

 2-200 amino acids long

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

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

 Receptors on target cell

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

 Ligand-receptor interactions are specific

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

 Number of receptors affects number of L-R

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

 L-R complex must be inactivated to allow

 Convert the change in receptor shape to an

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

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

 Ligand diffuses across cell membrane

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

 Ligand binds to transmembrane receptor

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

 Ligand binds to transmembrane receptor

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

 Ligand binds to transmembrane receptor

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

 Cells have receptors for different ligands

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

 Cell signaling is important for regulation of

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

 Pituitary gland secretes many hormones

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

 Extension of the hypothalamus

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

Hypothalamus synthesizes and secretes

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

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

 Insulin and glucagon are secreted by pancreas

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

Hypothalamic-pituitary axis stimulates the adrenal

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