Wednesday, November 4, 2009
BIO270 Lecture 3
- Welcome to Lecture 3. We have a few announcements before starting.
He is reminding us of wacky Wednesday – it’s a midterm break. The
other comment about the final exam. The final exam is essentially put
together – there will be 55 questions – you will have 2 hours to do it. 51
of those questions will be his, 4 will be from Dr. Forder. & we’re just
trying to get us more info for what to study. Are there any lab questions
on the final? Hmm he never thought of that, it’s a great idea. *Shouting
in background*. He’s kidding, traditionally the lectures & labs are kept
separate so no lab material is on the final exam – he understands we’re
all doing well on labs anyways.
- In the last couple of lectures we’ve been talking about all the
molecular components of how the endocrine system works so we should
all have a pretty good sense of what ligands are, receptors, signal
transduction pathways, different types of mechanisms. Also some of the
variability within that system. Remember all of these things are
controlled by genes – every one of them is slightly different, genes
occur in families, receptors, ligands all recur in different families. Now
because we know that hormones & signalling molecules are what create
what we are, & dictate how we’re going to act under certain
circumstances to a certain degree, we can get a sense of individual
differences amongst us.
- Next time we’re at a party & we see some unusual behaviour we can
say ah hah 5HT, I know what’s going on with you, whoa sex steroid
- You should have a sense of molecular variabilities – you know the
molecular components so you can practice amongst yourselves about
how these things differ & what he’d like to do for the first part of this
class is talk about how these circuits go together. We think of
neurological circuits & we know a little bit about the basics of that.
Endocrine circuits work the same way except they work over a great
distance. He’d like to go through some of the basics of what an
endocrine circuit is.
- He talked to some of us about our lab assignment & he understands
that we’re talking about reproductive cycles on that, so we’ll be delving
into the basics of that today so we get a sense of how these things work.
- Here are our readings. He doesn’t know what it is, but whenever we
get a textbook on this, it’s always scattered all over the place & we have
to look at different choices so it’s divided up into 3 chapters. The
amount of pages there is not too bad, but we’ll see where we are.
- Chapter 3 is what we’ve been working on & just really read the
overview here & up to regulation of glucose metabolism – we’re not
covering glucose metabolism in this lecture so you don’t need to do
- Chapter 4, we need to know a little about neuronal structure &
function because a great part of an endocrine circuit is a neuroendocrine
component so we need to know a little bit about the brain & a little bit
about the functional organization of the nervous system particularly the
peripheral nervous system as well. There is a fair amount of material
there but we’ll get a sense of what’s important after we go through this
lecture. - Now we’ve talked about the integration of signals from a cellular point
of view. When we look at it from an organismal point of view, we find
that the analogous systems are still there but they’re somewhat further
apart from each other & a little bit more complex, but the same idea
- Now as he mentioned, cell signalling is important for all physiological
processes – if cells couldn’t signal we’d never have come together as an
organism. In fact the evolution of cell signalling was probably one of
the first steps that had to occur before multicellular organisms came
together & even evolved a very important component of it.
- Now there are three components of these biological control systems
which is what our textbook calls it.
- The sensor system detects the level of the regulated variable so there is
perception that some things changes & it sends the signal to the
integrating center. For example, he sees something, it impinges upon his
retina, & that signal goes into integrative centers of the brain. There is
an integrating centre here that takes all that info from the sensor & other
sensors, compares it to past info, compares it on the physiological state
of the organ in question & on the basis of that, makes a decision &
sends a signal to the effector & the effector is the target tissue that
responds to the signal from the integrating signal.
- Every system that we look at will have these three components – it
won’t necessarily be a single organ system, it may be a multi-organ
system or a very complex set of tissues that are involved in this but
those three components will always be present.
- There are other things to think about.
- There is a set point. One of the themes of this course is homeostasis,
that is, that we have some sort of physiological limits within us that if
we go above or below those limits, it can be injurious to the body. There
is usually some sort of standard point that every organism has – it
differs from organism to organism, & even from person to person to
person there will be some slight differences. Some of us might be very
sensitive to stress, for example, some of us might be very resilient to
stress. There will be some sort of value of this variable that the body
will try to get to – if it’s too high it’ll try & bring it down; if it’s too low
then it will try to bring it up.
-A key point for any type of circuit & particular an endocrine circuit are
the concept of feedback loops. We talked a little bit about feedback
loops when we talked about autocrine & paracrine signalling. The
autocrine component was a feedback back to the cell to tell it how much
of the signal was released – if there wasn’t enough, then release some
more & if there’s too much, then shut it off. It works the same way
amongst these any kind of organism & any kind of endocrine pathway.
- In here, the output of the effector amplifies variable away from the set
point – what does that mean? Well he’ll give us examples of that.
- Positive feedback loops are not common in physiological systems.
He’s mentioning this b/c the book mentions this & he doesn’t agree with
that. He thinks that you would find that for every physiological system
there is a feedback loop – maybe we don’t define it in terms of an
endocrine system b/c maybe we haven’t described those particular
molecules as endocrine molecules yet, they are maybe not as well
defined in a physiological system, but they are there so just bear that in
mind. That is the type of question he won’t test us on. The book says
this but he thinks something else, what do we think? - So there is a positive feedback, & what they’re trying to say in a
simple language is, when you turn on the hormone, it hits the effector,
the effector sends another molecule back to send more of the effector. It
just comes back & says give me more, I love it. The negative feedback
loop is just the opposite, it goes back & says enough is enough, turn it
off. Positive feedback is give me more; negative feedback is turn it off.
Every system will have a combination of positive & negative feedback
loops & many times will be loops within loops – the more you start
looking the more loops you can find.
- Let’s take some simple examples. Here we have our endocrine gland –
it secretes into the bloodstream, it goes to the target organ, it causes the
release of something & it has a negative feedback & this is what we call
a direct feedback loop.
- By the same token it could be positive too but you get a sense for how
it works. One organ here, one organ there & then the feedback & there
could be an integrating system up there, is what they’re referring to.
- Okay let’s make it a bit more complex.
- Here we have a sense organ – he’ll say the olfactory system. Right
here, the sensory neuron, integrating center. He smells something, hey
what does that mean?
- When he was an undergrad, he was on the bus & he had this girlfriend
that used to wear this musk perfume, wild musk & he loved it & well
come on, 17, 18, you know. Sitting on the bus, he smelled exactly the
same stuff, & he thought wow this was fantastic so he turned around
very excitedly to see who was sitting beside me & it was this little old
lady about 80 years old wearing that stuff – he thought that should’ve
been illegal. This is an example of how a scent will bring back
memories, a lot of positive memories. Incidentally that ex-girlfriend of
his lives in Toronto & this took place in Winnipeg & everything follows
you, you just can’t escape.
- Then there will be the neuron here & that causes a second effect of the
target organ then you get a response & it feeds right back so there are a
number of stages in there.
- He thinks the book calls this the first order feedback loop – don’t you
love the way these things get so complex? - Now they make reference to a second order feedback loop.
- We’ve got another set of sense organ, sensory neuron, integrating
center, neuron here, endocrine gland & then it secretes the hormone into
the capillary, into the vascular system then it acts on the target organ &
then you get a response & finally you get a feedback.
- Frequently you can get a feedback at all levels but you can get a
couple of different feedbacks. In reality this is far more common than
this (above I think) – there are cases of this but usually we think of this
as a model first (left slide I think) when we look at a circuit we tend to
approach it with something fairly simple but once we start to look at it
we usually find that there is a number of effects.
- & then just when you thought it was safe to go outside again, we have
a third order feedback loop & it’s the same idea except that we’ve got a
double endocrine component so we have our neurological component
here, our sense system & nervous component, the neuroendocrine
component here & the first hormone is released & it works, it produces
an effect here, & then it has a secondary effect on a second hormone &
then that hits the target organ & you get a response that can affect it.
- Now in a number of complex systems, this is very common so some of
the endocrine systems that are, say involved in energy metabolism,
digestion, stress, they all involve several different organ systems. Ones
that are a little bit more simple, reproduction for example, although it’s
complex in some ways, it’s simpler in other ways because it is a
dedicated physiological system.
- Okay so the key component here is homeostasis. There are a number
of homeostatic control systems – one for all of the key aspects of your
body: calcium regulation, ion concentration, water concentration,
temperature, almost anything you can think of, not to mention virtually
most of the hormone systems that we think about.
- When you look at the entire system, there will consistently be sensors
& integrating centers & output pathways. But as we know, the more
complex the organ, the more sensory systems there are so we can get
into situations where olfaction, vision, tactility, gustatory senses, they
will all feed in to integrate so this integrating center can be really quite
- So for example if you were hungry, you might feel well, hungry, so
you go “Yeah I want to eat something”. On the other hand you may not
feel hungry, & you say “I feel tickady boo, I feel great” & somebody
puts delicious pizza in front of you & you smell it & it brings back these
memories of all these great times you ate pizza then suddenly you get
hungry, even though you don’t really need the food at the time, you start
to feel hungry. If you’re really hungry & then somebody brings the
pizza in, then you eat the pizza first before they have a chance to eat it
b/c you get really hungry – it has a synergistic effect. So all of this will
occur within these systems here.
- This is referring to the nervous system here obviously & by the same
token it applies to the endocrine system as well & obviously the more
interneurons, the more connecting neurons there are from a stimulus to
a response, to an effector, the more integrating systems there are going
to be & that just stands to reason, if you’re driving down the highway, the more interchanges there are that means the more greater city that
there is around you, same idea.
- Okay with the nervous system, we think of it as 2 parts & the reason
he’s going to this, we just can’t really discuss the endocrine without
really understanding a little bit about the nervous system. There are 2
components: the central nervous system & this is the brain & the
associated ganglia so brain, spinal cord for us. For a jellyfish, it’s the
ring nerve that they have, if you have a chance to look at jelly fish.
- Okay there is the sensory system that comes in so these are all the
different receptor systems that exist – anything you can imagine will all
come in through what are called afferent neurons, afferent projections,
they all come into the brain & there is an interneuron connecting & of
course these things will connect to how many other components within
the brain & then the efferent. Sometimes you get a mix-up b/w
afference & efference, they sound the same – he likes to think E for
exit, so if it’s exit that’s an efferent neuron, the afferent is the other one.
- Here is our stimulation, integration & there is our response here,
sensory, integration, output system.
- This component here is our peripheral nervous system – the
integrating system is the brain & actually if you look at the evolution of
the brain that is probably where it started. Initially, an organism simply
had to be able to move toward food or move away from something that
was damaging & then as the organism became more complex, it could
maybe perceive a food source through olfaction & then through say
photoreception & then it had to integrate those response. It then had to
integrate those responses with different motor pathways, so then as the
organism becomes greater & more complex, the integrating complexes
had to become more complex & then in the case of humans, we’ve got
all these memories & associative aspects of it that we have to consider.
- Somebody gives you a pizza – oh yeah but that’s from a pizza place I
hate, I’m not gonna eat that even though I’m starving, so that’s an
example of an association.
- He’s throwing this in to give us some indication that not all central
nervous systems are the same.
- In jellyfish, as he mentioned, there is a ring nerve & a nerve net. A
planarian here we have these two ventral nerve cords. What you see
here is that the brain nervous system kind of started around here (fear?),
it started to control the ability to take in food.
- Now we start getting a little more complex as we go to an annelid so
there is a brain & a whole variety of segmental ganglia.
- Then an arthropod here, a crab & an example of a mollusc,
cephalopod, the squid here, an echinoderm also has a sort of ring nerve
here & a number of ganglia here & of course us, you clearly recognize
us right as a vertebrate.
- There are a number of different designs of a nervous system & what
the brain is is a little bit different in different taxa but it all basically
works the same way, some are more complex but they all work in the
same way. - **He’s just going to throw this in – you don’t need to memorize
this**. He just thought we’d be interested in it. What we will see in so
many of our classes is the standardized human brain – we all know what
it looks like, we see it, there are pictures on the side of a bus, it’s in our
textbook, it’s on little icons on the computer screen, they’re
everywhere, we can see it in our sleep. That is a very unusual brain –
most brains don’t look like that.
- He just wanted to show us what a more typical brain is, so here is the
kind of mammalian brain with the large forebrain. There are just a
couple parts of the brain we should know & every vertebrate has the
same organization, a forebrain, a midbrain & a hindbrain. The
cerebellum is part of the hindbrain & here it’s nicely colour coded, the
yellow is the forebrain, the midbrain is red & the hindbrain is grey.
- Yeah let’s leave it at that, it’s a bit more complex than that but you can
see how structure varies from place to place. All the same components
are there, they just look very different, the same thing is done.
- He likes the shark brain the most because it’s got all the same parts as
the human brain essentially except for the huge neocortex & it’s all laid
out in a nice linear fashion – it’s a very nice brain to study.
- Anyways that is what brains look like.
- Let’s talk about the neuroendocrine system. What is a neuroendocrine
system? We know a little bit about nerve cells – a nerve cell connects to
another nerve cell; an endocrine cell puts its chemical signaling agent
directly into the bloodstream; but with a neuroendocrine system, it is a
nervous cell, a neurosecretory cell, that puts its components into the
- So this will be typically part of the brain. Here are the neurons here,
it’s getting inputs from other neurons, the neurosecretory cells &
they’re producing a number of neuroendocrine type agents, hormones,
signaling pathways. They usually have fairly long axons here with a
series of secretory terminals that will go into fenestrated capillaries, so
capillaries with holes in it, & we’ll talk a little bit more about that when
we talk about the pituitary gland, & then from here it will hit some sort
of endocrine tissue target tissue & you’ll get a feedback so it just brings
the two components together. It’s a nervous cell that is kind of acting
like an endocrine cell so hence the name neuroendocrine.
- This brings us to the pituitary because this is our classic example of a
- Pituitary gland consists of many, many hormones – it seems every
year we discover there’s more hormones in there. There are 2 basic
components that we’ll be dealing with mostly in this class & that's the
anterior pituitary so the adenohypophysis, sometimes he will call it the
pars distalis, its name in fish & other vertebrates, & the posterior
pituitary or the neurohypophysis. The hypophysis being the pituitary;
adeno being the anterior part & the neuro being the other part. It’s
called the neurohypophysis because the neurohypophysis, the posterior
pituitary, is attached directly to the brain.
- The adenohypophysis is actually not quite attached – it has a very
interesting different anatomical arrangement. - So posterior pituitary is an extension of the hypothalamus. When the
hypothalamus develops, so this is at the base of the brain, the
hypothalamus is one of the big integrating centres of the brain, it is
responsible for turning out a number of these key endocrine hormones
that turn on the various systems that we’re going to be discussing in this
class & so the neurons, originally they originate in the hypothalamus &
they send their axon terminals all the way down into this out pocketing
called the neurohypophysis & that is where they terminate. So the
neurohypophysis itself consists of nerve terminals, not so many cells
but nerve terminals, thousands & thousands of nerve terminals.
- The two hormones that are produced there that we’re mostly interested
in are variants of oxytocin & vasopressin – we’re going to be discussing
those hormones a fair amount over the next few weeks & they’re
produced in cell bodies in the hypothalamus, they travel down in
vesicles down the axons where they stay & are stored in the loose
terminals in the posterior pituitary.
- Your book likes to refer to this as the first order endocrine pathway in
the hypothalamus where the hypothalamus receives sensory input from
various sources & the hypothalamus, as he mentioned, is the integrating
- He’ll be giving us lots of examples of this & we’ll see it for virtually
every system we look at, so if the concept of the hypothalamus seems a
bit opaque right now, don’t worry about it, we’ll be going through this
in many different manners.
- The hypothalamus well it’s right under the thalamus – that is great if
you where the thalamus is, but if you don’t know where that thalamus is
then it doesn’t help us with the hypothalamus. Think of it as the base of
the forebrain & the hypothalamus is part of the forebrain.
- It is associated with homeostasis. It’s associated with the list in the
slide. Also associated with growth, stress, energy metabolism, anything
we can think of will be integrated in the hypothalamus – it’s a very
important part & a number of behaviours too are also associated with it
as well: feeding behaviour, some sexual behaviours, aggressive
behaviours can also be integrated in there, there are other places as well.
- It interacts very closely with the autonomic nervous system which
we’ll talk about in a moment.
- The whole concept of how the hypothalamus regulated the pituitary
was the subject of an incredible amount of debate in the early part of the
20 century. In fact the concept of the neurosecretory cell really wasn’t
known until about the 30s & a couple people (Angston, Bernstein,
Gerard, don’t know if they’re right, don’t think it’s important) almost
single handedly developed the notion by looking at the components in
insects & while they have very compelling evidence of the concept of a
neurosecretory cell, it took 20 years before anyone would accept it –
why the hell they looked at bugs, we’re not bugs, it’s different in
humans. That was part of the problem & eventually they persevered &
they’re considered to be the kind of godfather & godmother of the entire
system & that led the way to understand how neurosecretion could work
in the hypothalamus. There is a very interesting series of stories that go
along with that, not all of his stories are fun, there are some serious
- What he was going to say was that there were two key individuals, an
Andrew & a Rojas (not sure) who were very interested in trying to
purify these hormones of the hypothalamus that played a role in the release of pituitary hormones & interestingly, both were at McGill at
some point. Hans Selying was the person who came up with the concept
of stress. They passed through his laboratory & because the concept of
stress & the regulation of energy metabolism was considered to be so
important. The first bit of work was done on these hormones – now both
papers were published in 1955, one in the Canadian Journal of
Pharmacology & Physiology & the other one in the Journal of
Endocrinology. & then Rojas went to San Diego & Andrew went to
New Orleans & they started an absolute competition with each other for
the next several years. They eventually purified a number of these
things, purified them & they were both awarded the Nobel prize in
medicine in 1975 for all of their work there, but these laboratories
would spy on each other, they’d try to get the grad students drunk & get
information, it’s a tough world out there.
- Here is our standardized human brain. This is where the hypothalamus
is, just right up in this little region here. Below that is the pituitary. We
don’t think it’s very impressive when we look at it in this kind of scale,
but this little spot here is incredibly important & really acts as the
primary integration site for all of the sensory information that comes in,
associative information, to finally make a decision on the endocrine
response that the brain is going to have. The pituitary is very closely
associated with it & they have a very close association here.
- Now if we take a blow-up of the pituitary – this is again a human
pituitary. We have a series of neurosecretory cells here in the
hypothalamus, right around here. This is the optic chiasm here, they put
it there to help us orient it so this is where the visual information comes
into the nerve & this is where they cross over.
- So with these neurosecretory cells here, you can see in the
neurohypophysis they will send their nerve terminals right here into
- The other part of the pituitary which is the anterior pituitary is
anatomically separated from the rest of the pituitary so there is no direct
communication b/w the hypothalamus here & the adenohypophysis.
There is direct communication with the hypothalamus & the posterior
pituitary, but not the adenohypophysis. - So what happens is the factors of the hypothalamus have to be
released into a portal system, into the circulation, which carries it into
the pituitary, & then it diffuses out to affect the cells so a bit more
- The median eminence here is this region here. It’s called the median
eminence because if you look at the bottom of the brain, there is a
section that sticks out so that is an eminence & it’s right in the middle
so that is why it’s called the median eminence. This is where all of these
nerve terminals can converge here & it’s very highly vascularized & so
all of these terminals from various parts converge right there & put their
nerve terminals in what is called this portal system so they can percolate
down here into the adenohypophysis. So what is a portal system? A
portal system occurs in venous blood supply (blood returning to the
In the circulatory system of animals, a portal
venous system occurs when a capillary bed heart, in veins) so you have your arterial blood, arterial blood comes &
forms a series of capillaries in our tissues & then it drains & goes into
drains into another capillary bed through veins.the venous blood. When there is a secondary set of capillaries in the
Both capillary beds and the blood vessels that venous blood, that is called a portal system – nothing too mysterious
connect them are considered part of the portal about it, just a secondary capillary system that is downstream from the
venous system. primary one & there are a couple of examples of that. The hepatic portal
system is probably a bit more known.
- He mentioned that there are 3 lobes: the anterior lobe
(adenohypophysis) & the posterior lobe (neurohypophysis), but in some
organisms, there is an intermediate lobe here that releases just a couple
of different hormones.
- The intermediate lobe works the same way as the anterior lobe in that
it’s separated – there is no direct nervous connection – it has to receive
its input from the hypothalamus through these portal vessels.
- Now the adenohypophysis is the larger & the more elaborate of the
systems & have a number of hormones here: growth hormone,
prolactin, thyrotropin or thyroid stimulating hormone (TSH), follicle
stimulating hormone (FSH), luteinizing hormone (LH), &
adrenocorticotropin or (ATCH) & then we’re in the intermediate lobe –
here we have melanocyte stimulating hormone (MSH) – not so much of
a big thing for us as humans but if you are a dogfish shark or some other
type of fish that likes to change colour then it’s a fairly important
hormone. - They are, all of these, are responsible to be turned on or off by these
hypothalamic releasing factors. Now there are both, we always think of
them as releasing factors because the first factors that came out of the
hypothalamus that was associated with the regulation of the
adenohypophysis were releasing factors but since then we found out
that there are inhibitory factors as well so we can get a hypothalamic
releasing factor as well as a hypothalamic inhibitory factor. This doesn’t
hold for every system but