Lecture 9 Part 1
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Transcript of Lecture 9 Part 1
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Lecture 9 part 1
Intro to Endocrine
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Introduction
The nervous and endocrine systems coordinateall of the body systems The nervous system does so through the action of
neurons, and the neurotransmitters they secrete
Neurotransmitters regulate activity at synapses The endocrine system uses hormones produced by
endocrine structures that are released into theinterstitial fluid where they may enter the bloodstream and travel to distant sites in order to produce
their effects Both neurotransmitters and hormones exert theireffects by binding to specific receptors on target cells. Several mediators can act as both neurotransmitters and
hormones
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Hormones and their Receptors
Hormone
A mediator molecule that regulates the activity ofcells in the local environment, or in a distant part ofthe body
Hormone Receptor
A protein structure that a mediator molecule binds to
Can be on the cell surface or inside the cell
Receptor is specific for a specific mediator molecule Changes in the receptor due to binding of a hormone
or neurotransmitter cause changes in the cell
A target cell is a cell that has the receptor for a
specific neurotransmitter or hormone
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Types of Hormones
Main types of hormones
Autocrine
Paracrine
Endocrine
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Types of Hormones
Autocrine hormones local hormones that are secreted, and bind to the
same cell that secreted them causing a change in
that cell. Autocrine signals allow the cell to sense and
respond to a change in that cells environment
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Types of Hormones
Paracrine hormones local hormones that are secreted into interstitial fluid and
act on nearby cells
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Types of Hormones
Endocrine hormones secreted into interstitial fluid and then typically absorbed
into the bloodstream to be carried systemically to any cell
that displays the appropriate type of receptor
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Solubility of Hormones
Hormones can be divided into two broad
chemical classes.
This chemical classification is useful because the two
classes exert their effects differently
Lipid soluble hormones
bind to receptors in the cytoplasm or nucleus of the cell
Receptors inside the cell
Water soluble hormones
bind to receptors on the surface of the cell
Receptor is typically a G-protein
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Solubility of Hormones
Lipid soluble hormones
consist of steroid hormones, thyroid hormones,
and the gas nitric oxide
Steroid hormones are derived from cholesterol
Thyroid hormones (T3 and T4) are synthesized by
attaching iodine to the amino acid tyrosine
The gas nitric oxide (NO) is both a hormone and aneurotransmitter. Its synthesis is catalyzed by the
enzyme nitric oxide synthase
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Solubility of Hormones
Lipid soluble hormones require a carrier proteinfor transport in the watery environment of theblood Once they arrive at their destination, however, they
are able to freely pass through the plasma membraneto bind to receptors located in the cytoplasm or thenucleus of the target cell
When a lipid soluble hormone enters a cell and bindswith intracellular receptors (in the cytoplasm or the
nucleus), the activated receptorhormone complexalters gene expression: It turns specific genes of thenuclear DNA on or off.
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1 Lipid-soluble
hormone
diffuses into cell
Blood capillary
Target cell
Transport
protein
Free hormone
1 Lipid-soluble
hormone
diffuses into cell
Blood capillary
Activated
receptor-hormone
complex alters
gene expression
Nucleus
Receptor
mRNA
DNA
Cytosol
Target cell
Transport
protein
Free hormone
2
1 Lipid-soluble
hormone
diffuses into cell
Blood capillary
Activated
receptor-hormone
complex alters
gene expression
Nucleus
Receptor
mRNANewly formed
mRNA directs
synthesis of
specific proteins
on ribosomes
DNA
Cytosol
Target cell
Transport
protein
Free hormone
Ribosome
2
3
1 Lipid-soluble
hormone
diffuses into cell
Blood capillary
Activated
receptor-hormone
complex alters
gene expression
Nucleus
Receptor
mRNANewly formed
mRNA directs
synthesis of
specific proteins
on ribosomes
DNA
Cytosol
Target cell
New proteins alter
cell's activity
Transport
protein
Free hormone
Ribosome
New
protein
2
3
4
Lipid-Soluble
Hormone
Action
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2013 Pearson Education, Inc.
Slide 6Figure 16.3 Direct gene activation mechanism of lipid-soluble hormones.
The steroid hormone diffuses
through the plasma membrane
and binds an intracellularreceptor.
1
5
The receptor-hormone complex enters thenucleus.
The receptor- hormonecomplex binds a specific DNAregion.
Binding initiates transcriptionof the gene to mRNA.
The mRNA directs proteinsynthesis.
New protein
Nucleus
mRNA
DNA
ReceptorBinding region
Receptor-hormonecomplex
Receptor
protein
Steroidhormone Plasma
membrane
Extracellularfluid
Cytoplasm
2
3
4
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Solubility of Hormones
Water soluble hormones include peptide, protein, and amine hormones as well as a
group of local hormones derived from the arachidonic acid onour cell membranes called eicosanoids
Peptide hormones (3 to 49 amino acids long) and protein
hormones (50 to 200 amino acids long) are amino acid polymers Ex peptide: ADH and oxytocin
Ex protein: growth hormone and insulin
Amine hormones are derived from the modification of certainamino acids
Ex: catecholamines (epi and norepi) and histamine The two major types ofeicosanoids are prostaglandins and
leukotrienes both play a role in mediating the inflammatoryresponse
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Solubility of Hormones
Water soluble hormones are easy to transport
in the watery blood. The plasma membrane of
target cells, however, is impermeable to them Water soluble hormones exert their effects by
binding to receptors exposed to the interstitial
fluid on the surface of target cells The hormone binds to its receptor protein and causes a
change in that protein which activates a signal cascade
the hormone binding to its receptor acts as the first
messengerin a cascade of signal transduction
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Solubility of Hormones
The first messenger (the hormone) then
causes production of a second messenger
inside the cell, where specific hormone-
stimulated responses take place
One common second messenger is cyclic AMP
(cAMP).
Neuro-transmitters, neuropeptides, and severalsensory transduction mechanisms (vision) also act
via second-messenger systems
Fi 16 2 C li AMP d h i f t l bl h
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2013 Pearson Education, Inc.
Slide 6Figure 16.2 Cyclic AMP second-messenger mechanism of water-soluble hormones.
Recall from Chapter 3 that
G protein signaling mechanisms
are like a molecular relay race.
Hormone
(1st messenger)
Receptor G protein Enzyme 2nd
messenger
Adenylate cyclase Extracellular fluid
G protein (Gs)
GDP
Receptor
Hormone (1st messenger) binds
receptor.
Receptor
activates G
protein (Gs).
G protein
activates
adenylate
cyclase.
Adenylate
cyclase converts
ATP to cAMP (2nd
messenger).
Inactive
protein
kinase
Triggers responses of
target cell (activates
enzymes, stimulatescellular secretion,
opens ion channel, etc.)
Active
protein
kinase
cAMP activatesprotein kinases.
Cytoplasm
cAMP
GTP
GTP
GTP
ATP
1
2 3 4
5
Bl d ill
Bl d ill
Bl d ill
Bl d ill
Bl d ill
Bl d ill
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Water-soluble
hormone
Receptor
G protein
Blood capillary
Binding of hormone (first messenger)
to its receptor activates G protein,
which activates adenylate cyclase
Adenylate cyclase
Target cell
1
Water-soluble
hormone
Receptor
G protein
cAMP
Second messenger
Activated adenylate
cyclase converts
ATP to cAMP
Blood capillary
Binding of hormone (first messenger)
to its receptor activates G protein,
which activates adenylate cyclase
Adenylate cyclase
Target cell
ATP
1
2
Water-soluble
hormone
Receptor
cAMP serves as asecond messenger
to activate protein
kinases
G protein
Protein kinases
cAMP
Second messenger
Activated adenylate
cyclase converts
ATP to cAMP
Blood capillary
Binding of hormone (first messenger)
to its receptor activates G protein,
which activates adenylate cyclase
Adenylate cyclase
Target cell
ATP
1
2
3 Activatedprotein
kinases
Water-soluble
hormone
Receptor
cAMP serves as asecond messenger
to activate protein
kinases
G protein
Protein kinases
cAMP
Activated
protein
kinases
Second messenger
Activated adenylate
cyclase converts
ATP to cAMP
Activated protein
kinases
phosphorylate
cellular proteins
Blood capillary
Binding of hormone (first messenger)
to its receptor activates G protein,
which activates adenylate cyclase
Adenylate cyclase
Target cell
ATP
1
2
4
3
Protein P
ADP
Protein
ATP
Water-soluble
hormone
Receptor
cAMP serves as asecond messenger
to activate protein
kinases
G protein
Protein kinases
cAMP
Activated
protein
kinases
Protein
Second messenger
Activated adenylate
cyclase converts
ATP to cAMP
Activated protein
kinases
phosphorylate
cellular proteins
Millions of phosphorylated
proteins cause reactions that
produce physiological responses
Blood capillary
Binding of hormone (first messenger)
to its receptor activates G protein,
which activates adenylate cyclase
Adenylate cyclase
Target cell
P
ADP
Protein
ATP
ATP
1
2
4
3
5
Water-soluble
hormone
Receptor
cAMP serves as asecond messenger
to activate protein
kinases
G protein
Protein kinases
cAMP
Activated
protein
kinases
Protein
Second messenger
Phosphodiesterase
inactivates cAMP
Activated adenylate
cyclase converts
ATP to cAMP
Activated protein
kinases
phosphorylate
cellular proteins
Millions of phosphorylated
proteins cause reactions that
produce physiological responses
Blood capillary
Binding of hormone (first messenger)
to its receptor activates G protein,
which activates adenylate cyclase
Adenylate cyclase
Target cell
P
ADP
Protein
ATP
ATP
1
2
6
4
3
5
Water-Soluble
Hormone
Action
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Effects of Hormones
Prostaglandins (PGs) and leukotrienes are
eicosanoid hormones with local control. They are synthesized from membrane lipids and
have widespread effects PGs mediate pain, platelet aggregation, fever, and
inflammation. They regulate smooth muscle
contraction, gastric acid secretion, and airway size aspirin is a drug that works by inhibiting an enzyme
necessary for synthesis of certain PGs: the ones that
facilitate pain and the inflammatory response
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Effects of Hormones
Endocrine hormones control a variety of
physiological processes.
Among other things, they:
Balance the composition and volume ofbody fluids
Regulate metabolism and energy production
Direct the rate and timing ofgrowth and development
Exert emergency control during physical and mentalstress(trauma, starvation, hemorrhage)
Oversee reproductivemechanisms
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EFFECTS OF HORMONES(Interactions Animation)
o Introduction to endocrine hormones: Regulation,secretion and concentration
You must be connected to the internet to run this animation
http://www.wiley.com/college/tortora/0470084715/animations/anim_intro_horm_reg/screen0.swfhttp://www.wiley.com/college/tortora/0470084715/animations/anim_intro_horm_reg/screen0.swfhttp://www.wiley.com/college/tortora/0470084715/animations/anim_intro_horm_reg/screen0.swfhttp://www.wiley.com/college/tortora/0470084715/animations/anim_intro_horm_reg/screen0.swf -
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Endocrine System Glands
Glands that secrete endocrine hormones into
the bloodstream are called endocrine glands
They are one of two major types of glands in the
body, the other being exocrine glands (which
secrete their products into ducts)
We will focus on endocrine
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Hormone Interactions
Target cell responsiveness to a hormone
depends on three factors
Blood levels of hormone
Relative number of receptors on or in target cell
Influences exerted by other hormones and
molecules
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Hormone Interactions
Blood levels of hormone Increase in blood levels of hormone increase the likelihood of
hormone binding to receptor and causing effect
Relative number of receptors on or in target cell
Generally, a target cell has 2,000 to 100,000 receptors for aparticular hormone These receptors are constantly being produced and destroyed by the
cell
Hormones can influence the number of their receptors on atarget cell
Up-regulationtarget cells form more receptors in response to lowhormone levels
Down-regulationtarget cells lose receptors in response to highhormone levels
More receptors = more sensitive cell to hormone
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Hormone Interactions
Influences exerted by other hormones and molecules Lowered or increased binding affinity can result from multiple
causes such as pH changes, the presence or absence of specifichormones or cofactors, and even effects of second messengercascades.
A lowered affinity for binding may limit the effect of a hormone on itstarget cell
The actions of some hormones on target cells require asimultaneous or recent exposure to a second hormone
In this case, the second hormone is said to have a permissive effect
When 2 or more hormones act together to produce an effectgreater than either of them produce alone, the effect is said tobe synergistic
When one hormone opposes the actions of another, the twohormones are said to have antagonistic effects
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Control of Hormones
Release of most hormones occurs in short burstswith little or no secretion between bursts
When stimulated, an endocrine gland will releaseits hormone in more frequent bursts, increasingthe concentration of the hormone in the blood
In the absence of stimulation, bursts willdecrease in frequency causing blood levels of thehormone to decrease
Regulation prevents hormone levels being toohigh (overproduction) or too low(underproduction)
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Control of Hormones
Hormone secretion is regulated by;
signals from the nervous system (neural stimuli)
chemical changes in the blood (humoral stimuli)
other hormones (hormonal stimuli)
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Humoral Stimuli
Changing blood levels of ions and nutrients
directly stimulate secretion of hormones
Example: Ca2+ in blood
Declining blood Ca2+ concentration stimulates
parathyroid glands to secrete PTH (parathyroid
hormone)
PTH causes Ca2+ concentrations to rise andstimulus is removed
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Neural and Hormonal Stimuli
Nerve fibers stimulate hormone release Ex: Sympathetic nervous system fibers stimulate adrenal
medulla to secrete catecholamines
Hormones stimulate other endocrine organs to release
their hormones Hypothalamic hormones stimulate release of most
anterior pituitary hormones
Anterior pituitary hormones stimulate targets to secretestill more hormones
Hypothalamic-pituitary-target endocrine organ feedbackloop:
hormones from final target organs inhibit release of anteriorpituitary hormones
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Control of Hormones
Most hormonal regulatory systems work vianegative feedback, but a few operate via positivefeedback In a negative feedback system the hormone output
reverses a particular stimulus. For example:
Blood Ca2+ level is controlled by the parathyroid hormone(PTH). If blood Ca2+ is low, there is a stimulus for theparathyroid glands to release more PTH. PTH then exerts itseffects in the body until the Ca2+ level returns to normal. Ifthe level gets too high the body will cease PTH productionand secrete calcitonin lower the Ca2+ levels.
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Control of Hormones This example shows how PTH and calcitonin have negative feedback
influence on one another
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Control of Hormones
In a positive feedback system the hormone
output reinforces and encourages the stimulus.
For example, during childbirth, the hormone
oxytocin stimulates contractions of the uterus,and uterine contractions in turn stimulate more
oxytocin release, a positive feedback effect
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CONTROL OF HORMONES(Interactions Animation)
o
Hormones Summary
You must be connected to the internet to run this animation
http://www.wiley.com/college/tortora/0470084715/animations/over_hormones/screen0.swfhttp://www.wiley.com/college/tortora/0470084715/animations/over_hormones/screen0.swf