Chapter 3 - Cell Signaling and Endocrine Regulation

CHAPTER
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
Ligand binds to transmembrane receptor Catalytic domain of receptor starts a phosphorylation cascade Phosphorylation of specific intracellular proteins
Receptor Enzymes
Figure 3.20
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
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 affect 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

Chapter 3 - Cell Signaling and Endocrine Regulation

Uploaded by

Document Information

Original Description:

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Chapter 3 - Cell Signaling and Endocrine Regulation

Uploaded by

Copyright:

Available Formats

CHAPTER

Cell Signaling and Endocrine Regulation

PowerPoint Lecture Slides prepared by Stephen Gehnrich, Salisbury University

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

Cell signaling communication between cells

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

Types of Cell Signaling

Indirect Signaling Over Short Distance

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

Indirect Signaling Over Long Distance

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

Types of Cell Signaling

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

Opening and closing of gap junction can be regulated

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

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

Systems for indirect signaling have similarities and differences

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

Bind to transmembrane receptors

Rapid effects on target cell

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

Synthesis & Secretion of Peptide Hormones

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

Synthesis & Secretion of AVP

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

Synthesis of Steroid Hormones

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

Bind to intracellular or transmembrane receptors

Slow effects on target cell (gene transcription)

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

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

Some true hormones, some neurotransmitters, some both Most hydrophilic

Other Chemical Messengers

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

Other Chemical Messengers

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

Communication to the Target Cell

Receptor changes shape when ligand binds

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

A single cell may have receptors for many different ligands

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

Receptors can become saturated at high L

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

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

Changes in Number of Receptors

Target cells can alter receptor number

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

Changes in Number of Receptors

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

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

Inactivation of Ligand-Receptor Complex

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

Signal Transduction Pathways

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

Ligand-gated ion channels