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MBBS – Semester 1 Scenario 9, Workshop Activities

Activity 1: Control Systems – Nervous and Endocrine Control

In this activity you will compare the general “properties” of endocrine and nervous
control of body function.

Complete the table below to help you draw broad comparisons of the nervous and
endocrine systems with respect to a number of conceptual elements.

Nervous System Endocrine System


Target Diversity Nerves, muscle cells and Basically every cell is
Identify the diversity of glandular epithelial cells regulated by secreted
target tissues/cells. are direct targets of chemical messengers
That what “types” of nerves
cells/tissues are
targets?
Provide examples
Spatial Relationship Close anatomical The cell secreting the
The relationship localization of the site of chemical messenger can
between site of release (from axon be in a different tissue is
chemical messenger termini) and the target a different region of the
release and target cell – i.e. the synapse body to the target – with
the chemical travelling
via the circulation to
reach target
Regulation of Anatomical targeting Regulation of which
Response and release of a small cells will respond is
The importance of amount of messenger primarily determined by
regulation of receptor are more important in regulating expression of
expression and other regulating which cells the receptor
aspects that can respond rather than
control which regulation of which cells
cells/tissues respond are expressing the
receptor
Speed of response – Fast responding Slower response
onset of action

Duration of General short duration Generally more


response prolonged duration

Specificity of Specificity due to Specificity due to


response receptor receptor
MBBS – Semester 1 Scenario 9, Workshop Activities

Activity 2: Hypothalamo-Pituitary Axis

In this activity you will explore the structural and functional relationships within the
hypothalamo-pituitary axis.

Label the diagrams below with respect to the following questions.


(Note: another copy of the diagram is available on the following page if needed.)

1. Site of GnRH synthesis


2. Site of GnRH release from the “signaling cell”
3. Site(s) of action of GnRH
4. Site containing cells that express the receptor for GnRH
5. Site of cells that synthesise LH and FSH in response to GnRH
6. Site where ADH is synthesized
7. Site where ADH is released
8. Site(s) of release of neurocrine secretions
9. Circle the “component” in the diagram that is the “true” endocrine structure of
the hypothalamo-pituitary axis

6
, 1
4
,
,
2
4
,
5

3 4 5 8
7
, ,
9 , ,
,
4 ,4 4 4
4
, ,
4 , ,
,
, , , ,
,
4 ,4 4 4
4
, ,
4 , ,
,
5 5
, 5 5
5
5
MBBS – Semester 1 Scenario 9, Workshop Activities

Activity 3: Concepts of Complexity and Regulation of Cell/Tissue/Organ


Function

Use the diagram below think about the ‘concepts” that underpin the questions
provided.

1. How complex is chemical communication? Where can chemical communication


potentially go wrong?
Using the example above estimate the number of discrete steps/events in the
communication process. List up to 10 steps/events.

At the level of very discrete “steps” there would be hundreds to thousands.


For example just the the synthesis of insulin involves all of the steps of
transcription, translation, post-translational modification, packaging in the
rough ER and gogli and then steps in secretion. There are even “steps”
associated with insulin circulating though the blood as there are binding
proteins produced in the liver, released into the blood that bind to insulin
and in part ensure that insulin is not filtered by the kidney to quickly
Key take home message is that there are many many steps each of which is
required and important and for many of the steps there is a sequential
interdependence i.e. step A must occur before step B
MBBS – Semester 1 Scenario 9, Workshop Activities

2. Depending upon the “nature” of the malfunction (breakdown) in a chemical


communication process do you think there might be potential for a different
spectrum of effects on body and/or cell function? Try and explain your thinking.
Yes – concept here is that the more “central” or higher up in the sequential
nature of the process the more wide spread is the potential for dysfunction.
Thus at one extreme of the concept is if the pancreas stops producing insulin
then all of the insulin sensitive tissues cannot function normally leading to
wide spread whole of body dysfunction. An example at the other extreme
might be if 1 cell in the liver does not express the receptor for insulin that 1
cells function will not be normal but that would have no consequences at the
level of the function of the liver or any other system etc in the body

3. Do you think there might be limitations for treatment of the underlying cause of a
disease dependent upon the “nature” of the malfunction in the chemical
communication processes? Why?
(Hint: Think about the “cause(s)” and treatments of diabetes type 1 vs type 2)
Yes: remember the discussion about it being easier to treat an endocrine
disease if the hormone is missing by simply providing an exogenous source
of the hormone (could be injection by pill etc) replacing what is missing,
alternatively if the problem is due to lack of receptor expression it is very
difficult to replace the receptors – rather we try and manage the
consequences of not having any receptors being expressed
MBBS – Semester 1 Scenario 9, Workshop Activities

Activity 4: Modes of Communication

Use the diagram above answer the following questions.

1. List all of the chemical messengers depicted in the diagram – you should be
able to find at least 5 and maybe there is even a 6th.
GnRH, FSH, LH, inhibin, testosterone even ABP could be consider to be
a chemical messenger
2. List the chemical messenger(s) involved in an endocrine mode of
communication.
FSH, LH, some of the actions of testosterone are via an endocrine mode
(e.g. testosterones action on skeletal muscle metabolism)

3. List the chemical messenger(s) involved in a neurocrine mode of


communication.
GnRH
4. List the chemical messenger(s) involved in a paracrine mode of
communication.
Testosterone: the actions of testosterone within the testis/seminiferous
tubule are examples of paracrine communication
MBBS – Semester 1 Scenario 9, Workshop Activities

5. List the chemical messenger(s) that are involved in more than one discrete
mode of communication at the same time.

Testosterone is the best example

Activity 5: Receptors and Intracellular Signaling Cascades

Examine the diagram below to identify the key elements, then try and answer the
questions.

1. What class/family of receptors is involved in the regulation of the secretory


response?

G protein linked receptor

2. Draw an arrow to identify the intercellular signal?

The chemical messenger is the inTERcellular signal

3. Name the secondary messenger involved?

cAMP

4. List the component that synthesises the secondary messenger?

Adenylyl cyclase
MBBS – Semester 1 Scenario 9, Workshop Activities

5. List the components of the signalling cascade that are directly interconnected
by the G protein.

The receptor and adenylyl cyclase

6. Briefly define the role of the G protein in this process.

To transfer the signal from the activated receptor to adenylyl cyclase


resulting in activation the adenylyl cyclase

7. Circle or indicate the elements/components of the pathway that would need to


be turned off in order for secretory activity to decrease/stop.

Everything that is turned on must also be turned off

Activity 6: Clinical Relevance: Bacterial Toxins Can Alter Regulation of cAMP


production

Using the diagram above try and answer the following questions.
MBBS – Semester 1 Scenario 9, Workshop Activities

1. Briefly explain how the action of cholera toxin results in excess secretory
activity of intestinal epithelial cells contributing to the excessive watery
diarrhoea characteristic of cholera.
The toxin “bypasses” the need for the G protein coupled receptor to be
activated and instead directly activates the stimulatory G protein which
then simulates adenylyl cyclase to increase cAMP which ultimately
triggers increased secretion

2. Briefly explain how the action of pertussis toxin results in excess secretory
activity of bronchial epithelial cells contributing to the wet hacking cough
characteristic of whopping cough.
The toxin inactivates the inhibitory G protein such that even if the G
protein coupled receptor is activated it will NOT activate the inhibitory G
protein and thus adenylyl cyclase activity can NOT be turned off leading
to uncontrolled cAMP production and uncontrolled secretion
MBBS – Semester 1 Scenario 9, Workshop Activities

Activity 7: Clinical Relevance Example 2 – Growth Factor Stimulation of Cell


Division

Use the diagram above to answer the following questions.

1. What class/family of receptors is involved in the transduction of the signal from


the intercellular signal molecule?
Enzyme linked receptor
2. Identify two sites of signal amplification in the intracellular cascade.
Any of the steps that involves an enzyme e.g. MAP-kinase-kinase-kinase
or MAP kinase-kinase or MAP kinase
3. What acts as the “molecular switch” to activate MAP-kinase-kinase?
phosphorylation
4. If activation of gene regulatory proteins A & B results in activation of epithelial
cell proliferation what would be the effect of a mutation in the Ras gene that
prevents Ras protein from deactivating?
The pathway that stimulates cell proliferation will not be turned off
5. If the outcome of activation of this intracellular signaling cascade is increased
cell proliferation what components of the intracellular signaling cascade would
need to be “turned off” in order to stop cell division? Circle them on the
diagram.
MBBS – Semester 1 Scenario 9, Workshop Activities

All the parts that had been turned on need to be turned off to stop cell
division

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