Welcome to ANP 214

1
Welcome to ANP 214 Fall Quarter

• Agenda
• Introduction and syllabus (always so exciting)
• WebCT
• Attendance, and How-likely-it-is-that-you-might
  -be-able-to-add-this-course-if-you-arent-already
  enrolled
• Chapter 18 Part I- Endocrine System

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Chapter 18- The Endocrine System Part 1

• Homeostasis
• Nervous system versus endocrine system
• Cellular communication
• Hormone classes
• Mechanisms of hormone action

3
Homeostasis

• Homeostasis-
• Significance of maintaining homeostasis?
• Examples
• Both the endocrine system and nervous system play
  important roles in maintaining homeostasis

4
Homeostasis and Feedback Loops

• All systems involve three components a
  receptor, a control center and an effector

Stimulus (input into the system)
RECEPTOR (ie. Osmoreceptor of hypothalamus)
CONTROL CENTER(such as the brain)
EFFECTOR(such as a organ, muscle, gland)
Response(systems output)
The response to the stimulus leads to change.
The change is fed back to the receptor.
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Homeostasis and Feedback Loops
Stimulus (input into the system)
RECEPTOR (ie. free nerve ending in the skin)
CONTROL CENTER(such as the brain)
EFFECTOR(such as a muscle, or a gland)
Response(systems output)
The response to the stimulus leads to change.
The change is fed back to the receptor.

• In negative feedback a stimulus causes a response
  which works to reduce the stimulus
• Stabilizing
• Examples?
• In positive feedback a stimulus causes a response
  which further increases the stimulus
• Examples?

6
The nervous system and endocrine system both work
to maintain homeostasis

• Nervous System- monitors a few, specific cells or
  groups of cells at a synapse, and elicits
  responses that are rapid, specific, and short in
  duration
• Endocrine system- slow and steady
• Works via long term co-ordination of cellular
  activity throughout the entire body
• Growth, development, reproductive capabilities,
  metabolic rate

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Recall that in the Nervous System

• The NS is in charge of regulating split-second
  situations
• Examples?
• Response is fast!
• Neurotransmitter (NT) signals released into
  synapse
• Many NT receptors encountered in ANP 213 were
  ion channels (but not all)
• Utilize synaptic transmission (communication)

8
General characteristics of the Endocrine System

• Chemicals released by cells enter the bloodstream
• Targets specific cells or groups of cells or
  entire organs
• Often regulated by negative feedback
• Goal is to preserve homeostasis

From thyroid
To cells of toe
bloodstream
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In general, how do cells communicate?

• Direct Communication-(specialized and rare)
• Numerous gap junctions connect neighboring cells
• Indirect Communication- most cellular
  communication, involves release and receipt of
  chemical messenger

Cell 1
Cell 2
Cell 1
Cell 2
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Two Types of Indirect Communication

• Paracrine- communication from cell to cell within
  a single tissue (aka. CLOSE together)
• -Messenger is released into extracellular fluid
  (ECF), thus typically effects are only local
• Endocrine- hormones released from one cell acting
  at cell(s) of distant tissue(s)

Cell 1
Cell 2
Cell 2
Cell 1
bloodstream
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Lets pause and review

• Most cellular communication, involves release
  and receipt of chemical messenger
• How does release occur? Whats involved?
• How does receipt occur? Whats involved?
• Chemical messengers? Nervous system examples
  anyone?

Cell 1
Cell 2
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In the Endocrine System

• One hormone may have effects on more than one
  cell type (think receptors!)
• Effects may have fast or slow onset with short or
  long duration (from seconds up to days or longer)
• One cell can respond to numerous different
  hormones (think receptors again!)
• Thus, endocrine system well suited for regulating
  gradual and coordinated processes

13
One hormone may have effects on more than one
cell type
One cell can respond to numerous different
hormones
Hormones
Receptors
cell type 1
cell type 2
cell type 3
Effects may have fast or slow onset with short
or long duration
Stimulation of this receptoraffects
transcription of that same enzyme
Stimulation of this receptor activates an enzyme
enzyme
Gene for enzyme
14
Endocrine System

• Includes all endocrine cells and tissues of the
  body the produce hormones or paracrine factors
  with effects beyond their tissue of origin
• Can you think of some examples?

15
Organs and Tissues of the Endocrine System
Lecture Lab
ADIPOSE TISSUE
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Two types of glands in the body

• Exocrine glands- secrete products onto epithelial
  surface through a duct
• Can you remember any examples?
• Endocrine glands- release hormones into the blood
  or lymphie pituitary, pancreas, thyroid
• NOTE Some organs are solely endocrine in
  function, while other organs have endocrine
  function as an additional function, in addition
  to others, ie pancreas

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Hormones

• A compound that is secreted by one cell and
  travels through the circulatory system to affect
  the activity (function, metabolism, growth, etc.)
  of cells in another part of the body.

Huh, and I thought it just meant estrogen and
testosterone.
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Hormones are classified based on their chemical
structure

• Amino acid derivatives
• Peptide derivatives
• -Two groups
• Lipid derivatives
• -Two groups

Epinephrine, Dopamine, etc.
AA 1
AA 3
AA 3
AA 4
Cholesterol
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Amino Acid Derived Hormones

• Tyrosine is the precursor for the catecholamines
  (NE, Epi, Dopamine) and thyroid hormones
• Tryptophan is the precursor for serotonin, and
  hence melatonin

Did you notice that these compounds can be called
neurotransmitters OR hormones? How do we know
what to call them??
20
Recall that peptides and proteins are polymers of
amino acids
Growth Hormone (GH)
Growth Hormone (GH)
Zoom-in
Growth hormone receptor
Amino Acid 1
Amino Acid 2
Amino Acid 3
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Peptide Derived Hormones
Dont focus on these differences, just appreciate
that these hormones are chains of amino acids
encoded for by genes! These do not come about by
way of the diet, but by way of the nucleus and
the ribosome!

• Glycoproteins
• 200 AA long, with lots of attached sugar moieties
• Diverse group
• From 9 AA to small proteins
• ADH, oxytocin (short)
• GH, PRL, etc

receptor
many steps
ADH rna
ADH
Gene for ADH
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Lipid Derived Hormones

• Steroid hormones (from cholesterol) - Released
  from reproductive organs, adrenal glands
  (corticosteroids) and kidneys (calcitriol)
• Eicosanoids (from arachadonic acid)
• -Membrane lipids function as signaling molecule
  precursors! Wow, thats wild!

Phospholipid bilayer
prostaglandins
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Hormones en route

• Some hormones circulate freely in the bloodstream
• Effects may last for minutes to hours
• Demise- Bind receptors, broken down at liver or
  by circulating enzymes
• Some hormones travel through blood tightly
  bound-up by transport proteins or binding
  proteins (BPs)
• Steroid hormones, thyroid hormone
• Longer lasting effects
• However they may travel, hormones only start
  having an effect when they do WHAT?

bloodstream
Endocrine Cell
BP
As-is
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Hormone Receptors
Hormone binding an intracellular receptor

• To have an effect, hormone must bind and activate
  a RECEPTOR
• Hormone receptors may be located at the cell
  membrane OR in the cytosol!

Hormone binding an extracellular portion of a
transmembrane receptor
hormone
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Hormone Classes

• Amino acid derivatives
• Peptide derivatives
• Lipid derivatives
• Which of these hormones (signals) do you think
  are likely to work extracelluarly, and why?
• Which of these hormone classes do you think could
  work from inside of the cell, and why?
• Hint Think about their chemical structure

26
Hormones receptors

• May be located within the cell (in the cytoplasm
  or nucleus)
• Which hormone classhas this type of receptor?
• -Or -
• Located at the cell membrane -Which hormone
  classhas this type of receptor?

27
This is a short, and intentionally ambiguous list
of what hormones may do at a target cell

• Indirectly open membrane ion channels
• Turn a cytosolic enzyme on or off
• Stimulate synthesis of an enzyme or structural
  protein
• Increase or decrease the rate of synthesis of a
  protein or enzyme

Cell 2
Cell 1
bloodstream
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Some hormones bind to intracellular receptors

• Lipid derived hormones diffuse across the bilayer
  and bind to cytosolic or nuclear receptors!
• Once inside the cell, these hormones primarily
  affect transcription of genes!!

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• What might you predict about the response time?
• The duration of the effect?

Steroid Hormone animation
30
How do amino acid and peptide hormones work?

• Do these signal molecules enter the cell?
• Do these hormones work directly or indirectly on
  their target cells?

31
Many hormone receptors are G-Protein Coupled
Receptors (GPCRs)

• GPCRs are a family of membrane receptors that
  have a common 3-D structure
• These protein receptors zig-zag across the
  membrane 7 times
• GPCRs are transmembrane receptors that associate
  with a cytosolic G-proteins

G
G-protein
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Hormones can initiate a signaling cascade
within the target cell

• The hormone is considered the FIRST messenger
• The binding of the hormone to its membrane
  receptor activates a G-protein
• The activated G-protein then activates a SECOND
  messenger
• calcium ions (Ca2)
• cyclic AMP (cAMP)
• cyclic GMP (cGMP)
• Importantly, the original signal is greatly
  amplified

G
cAMP
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Signaling Cascade
Peptide Hormone
First Messenger
GPCR
G
G-protein
? cAMP
Second Messenger
animation

• GPCR animation http//entochem.tamu.edu/G-Protein
  /index.html

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Signaling Cascade or Signal Transduction

• Fancy terms for this signal relay that occurs
• Note that the signal is physically transduced
  across the lipid bilayer
• Usually, signal is amplified at level of second
  messenger
• ie. Release of many calcium ions from
  intracellular stores as the result of one hormone
  molecule binding
• Where have you seen intracellular stores of Ca2
  before?

35
G-proteins are the link between the 1st and 2nd
messengers

• G proteins have three subunits and are associated
  with GPCRs (G protein coupled receptors)
• G-proteins exchange GDP for GTP upon receptor
  activation
• Upon activation, G protein subunits released and
  then mediate variety of intracellular effects

36
I know you are just dying to ask, But, Heidi,
what might a released G-protein subunit do?

• I have to give you the stock answer that, well,
  its complicated.
• Depends on what flavor of G-protein is
  activated
• The three flavors or subtypes to know are
  Gs, Gi, and Gq
• THM different G proteins affect levels of 2nd
  messengers in different ways

This info is NOT in the textbook!
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Classes of G-proteins

• Gq - Ca2 mobilizer, causes release of Ca2 from
  cytosolic storage
• Gs - stimulatory, activation leads to ? in
  Adenylate Cyclase (AC) activity, thus ? cAMP
• Gi - inhibitory, ? activity of AC, ?in cAMP
• Also leads to opening of K channels
• What effect does this have on excitable cells,
  like neurons?

Gs
Gi
Gq
or
or
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How do the levels of 2nd messengers in the cell
change? And what would be the downstream
effects?

• Remember the 2nd messengers calcium ions
  (Ca2)
• cyclic AMP (cAMP) cyclic GMP (cGMP)

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How is Ca2 mobilized?

• Where might calcium come from?

Gq
Ca2
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Effects of Elevated Calcium

• High intracellular Ca2 activates kinases
  (molecules that phosphorylate other molecules)
• Kinases relays the message by activating other
  enzymes
• Phosphorylation cascade!
• Possible result of elevated calcium
  Exocytosisor contraction, etc.

Yikes!
41
An example

• During the flight or fight response (activation
  of the sympathetic nervous system), what happens
  to the amount of blood flow to the skin?
• How does this actually happen?

Hormone

• You fill in the details.
• Hormone(s)? _____
• Cell type? _____
• Type of G protein?___
• Second messenger? ___
• Effect? _______

a cell
G?
Numerous steps
42
What happens when a Gs or Gi linked GPCR is
activated?

• Ultimately, the second messenger affected is a
  molecule called cAMP (a derivative of ATP)
• Activation of Gs increases cAMP activation of Gi
  works to decrease cAMP levels
• cAMP activates kinases to initiate
  phosphorylation cascades in a cell

43
Adenylate Cyclase (AC) affects cAMP levels

• AC is a membrane associated enzyme that catalyzes
  the conversion of ATP to cAMP
• AC is activated (stimulated) by Gs subunits
• AC is inhibited by Gi subunits

Adenylate Cyclase
Gs
Gi
ATP
44
What affects might elevated cAMP have in a cell?

• Depends on the cell, but in general, cAMP
  activates kinases.
• These kinases go on to phosphorylate downstream
  effectors, enzymes or ion channels
• A phosphorylation cascade

• Activation of enyzmes
• Cellular response

45
Another example of GPCR activation

• You are being chased by a large, scary bear
• What branch of the nervous system is activated?
• How does this relate to the endocrine system?
• What will happen at your liver cells as a
  consequence of this activity?
• What is REALLY happening at your liver cells?

?
Liver cell
?
glycogen
glucose
Liver animation
46
AC
Gs
Gq
Gs
Replace this,with this
Gi
Gi
ATP
47
What have we covered so far?

• Hormones can activate intracellular receptors or
  membrane receptors
• Many membrane receptors are GPCRs
• Hormones that bind to membrane receptors initiate
  a multi-step cascade of events INSIDE of the
  cell, via activation of a G protein
• G proteins come in different forms (Gs, Gi, and
  Gq). Activation of different G proteins affect
  different cellular Second messengers.
• Such as?
• Typically, somewhere along a G-protein mediated
  cascade of events, a KINASE is activated
• Phosphorylation and dephosphorylation serve as
  rapid on-off switches for numerous enzymes
• Activation of cellular enzymes can alter cell
  processes, such as metabolism, mitosis,
  migration, gene expression, etc.

Sheesh, is that all?