Chapter 3 - Cell Signaling and Endocrine Regulation

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

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3C H A P T E R

Cell Signaling and Cell Signaling and Endocrine Regulation Endocrine Regulation


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

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin CummingsFigure 3.1

Types of Cell Signaling


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


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

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin CummingsTable 3.1

Indirect Signaling


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


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


Synthesis & Secretion of AVP


Transmembrane Receptor


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


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


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


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





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


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

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin CummingsFigure 3.13a

Changes in Number of Receptors

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin CummingsFigure 3.13b

Ligand-Receptor Dynamics

Affinity of receptor for ligand affects number of L-R complexes Higher affinity

constant (Ka) response


Inactivation of Ligand-Receptor Complex

L-R complex must be inactivated to allow responses to changing conditions


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


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


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


Changes in Gene Transcription


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


Receptor Enzymes

Ligand binds to transmembrane receptor Catalytic domain of receptor starts a

phosphorylation cascade Phosphorylation of specific intracellular proteins


Receptor Enzymes


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


Second Messengers


Inositol-Phospholipid Signaling


Cyclic-AMP Signaling


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

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


Posterior Pituitary


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


Hypothalamus and Anterior Pituitary


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


Antagonistic Regulation of Blood Glucose


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


Control of Glucose Levels in Arthropods

Crustacean hyperglycemic hormone (CHH) Neurohormone from

crab eyestalk Secreted in response

to low glucose in blood/hemolymph


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




Adrenal Tissue in Different Vertebrates


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

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Chapter 3 - Cell Signaling and Endocrine Regulation