lecture 9 part 1

7/30/2019 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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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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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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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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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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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




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




Adenylate cyclase

Target cell

ATP

1

2

3 Activatedprotein

kinases

Water-soluble

hormone

Receptor


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




Adenylate cyclase

Target cell

ATP

1

2

4

3

Protein P

ADP

Protein

ATP

Water-soluble

hormone

Receptor


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




Adenylate cyclase

Target cell

P

ADP

Protein

ATP

ATP

1

2

4

3

5

Water-soluble

hormone

Receptor


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




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
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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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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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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

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