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Course: Health and medicine > Unit 1
Lesson 4: Endocrine system introductionCellular mechanism of hormone action
Learn about the interaction between chemical messages and their target cells in this video about hormone action. By Ryan Patton. . Created by Ryan Scott Patton.
Want to join the conversation?
- this may sound really dumb but what happens to the excessive amount of cAMP that stays in the cell?(15 votes)
- the excessive cAMP eventually undergoes decomposition into AMP, in which it is catalyzed by the enzyme phosphodiesterase.(44 votes)
- So is a G Protein a secondary messenger? (Just asking b/c a video I watched on Youtube said that it wasn't.) It seems like it should be a secondary messenger, but then again it's attached to the cell membrane, so I don't know.(5 votes)
- No, G Protein is not a secondary messenger. As you pointed urself, second messenger's are the once's that are free to move inside and outside the cell, and G proteins are membrane anchored proteins. Basically, G protein gets activated as a appropriate ligand ( a neurotransmitter or a hormone) comes and stimulates its receptors i.e The G-Protein Coupled Receptors. Upon stimulation, G proteins activate either adenyl cyclase which produces cyclic-AMP or they stimulate phospholipase C which makes Inositol triphosphate or IP3. These molecules, IP3 and Cyclic-AMP are the so-called second messengers because they amplify the signalling cascade initiated by a primary signalling messenger which is the ligand in this case. Now these second messengers are free to move inside the cell and they have their specific intra-cellular targets upon which they work on. Other examples of second messengers are Nitric Oxide, DAG i.e Diacyl Glycerol, Calcium ions and Ceramide. I hope its helpful. :)(31 votes)
- What do the 2 extra phosphates do after ATP is converted to cAMP? Do they hang around to attach to a guanine before it attaches to the G protein? Also, how does the receptor happen to switch the GDP to GTP?(5 votes)
- The two extra phosphates are bound together. It's a compound known as pyrophosphate. Pyrophosphate is able to provide energy in the cell when they disassociate, like ATP. These phosphates could be used to make many things like GTP or ATP.
A protein called a transferase switches out GDP for GTP on the G-Protein when hormone is bound to the receptor. The hormone changes the conformation, or shape, of the receptor to make the GDP accessible to the transferase.(7 votes)
- How do primary messenger hormones choose which cells to get into? As I understand it hormones are discriminated by receptors, but if they have to get into the cell to find the receptor, if there is no receptor they just exit the cell or is there a way for the hormone to avoid entering a cell with no specific receptor for it.(6 votes)
- Primary messenger hormones only choose the targeted cells which have to give a message, they have also specific receptors on the cell surface helps to recogenise specific cell or targeted cell.(2 votes)
- So can some thyroid and steroid hormones cross the cell membrane but not the nuclear membrane?(3 votes)
- If you look at a diagram of a cell, the Nucleus is surrounded by the Endoplasmic Reticulum, containing a bunch of folds that looks like a labyrinth, which makes it really hard for large molecules to penetrate, secondly, the nuclear membrane is a double-folded cell membrane with pores that are very small, making it harder, even for lipid-based molecules like hormones, to go through. So with that much work for a hormone to trigger a response, it'll certainly take a long time for it to go into the nucleus and to trigger a response, however there are receptors on the ER that are specific to hormones (generally named Intracellular Receptors) which then triggers Transcription proteins that are already found within the nucleus for gene expression. Hope this makes sense!(5 votes)
- Are steroids amphipatic? If not, how are they transported through our blood? I know that lipids (triglycerides, to be specific) are transported inside chylomicrons through the blood, but I'm not really sure if steroids are packaged in the same way.(2 votes)
- They are carried in the blood by binding to carrier proteins.(4 votes)
- why are water-soluble hormones consider as fast-acting than lipid-soluble hormones?(0 votes)
- Water-soluble hormones are typically peptides, which means they used a cell surface receptor to create their action. Epinephrine, for example, is a peptide hormone that acts instantaneously due to its ability to create a large response inside the cell. The surface receptors can activate the needed proteins quickly because they are already produced and present within the cytoplasm.
Lipid/cholesterol hormones are intracellular hormones. They are able to pass through the cell's lipid bilayer, but once in the cytoplasm have to bind with their receptor and then get shuttled into the nucleus. These are "slow-acting" hormones because they act as transcription factors, causing certain genes within a cell to turn on or off. This process of transcribing DNA and then translating the mRNA into a new protein takes time, and its effects aren't always immediate. Cortisol, a glucocorticoid, is a common drug that is given that has long-lasting side effects due to the over-activation of certain genes.(8 votes)
- In terms of amplification, does Ryan mean that one ligand binding to a receptor causes the conversion of ATP to cAMP by one adenylate cyclase multiple times OR that the ligand causes a cascade of multiple adenylate cyclases converting ATP to cAMP.(2 votes)
- https://www.nature.com/scitable/topicpage/cell-signaling-14047077
This link is to a lovely article with diagrams. Here they will explain that one ligand, such as a neurotransmitter or hormone, is the first messenger that causes the formation of one ATP. One ATP then creates multiple cAMP second messengers. Those cAMPs are activating hundreds of enzymes or protein kinases. Those protein kinases are able to facilitate thousands of the same chemical reactions. That is called amplification. Check out the Nature article It is very nice!(4 votes)
- So cAMP activates protein in the cell, but so what? What does activating protein have to do with the end hormonal response - what is actually changed?(1 vote)
- The activated protein will then carry out some vital function within the cell. This could range from DNA regulation to enzyme activity etc.(4 votes)
- Does the hormone "Serotonin" takes the primary means to travel to its receptors or a secondary ?(2 votes)
- Serotonin mainly uses receptors that activate secondary messengers. However, there is one type of serotonin receptor called the 5-HT3 receptor, which starts acting more like an ion receptor when activated by serotonin. These types of receptors are called Ligand-gated ion channels.(1 vote)
Video transcript
After coursing throughout the
blood vessels of our bodies, a hormone eventually
meets a receptor that was created specifically
for it by the target cells that it was sent to stimulate. And the way that hormone
interacts with the receptor happens in one of two
very characteristic ways. And I want to show you
today how that happens. And so the first major
mechanism of hormone action at the cell that I'm
going to start with is by secondary messengers. And I'm going to start
with secondary messengers because, historically, they're
a little bit more confusing. But essentially what's
happening is a hormone is binding to a
receptor on a cell. So let me draw a cell
and its receptor. And I'll draw a
hormone binding to it. But the process of that binding,
instead of just stimulating the effect, it really sets
off this chain reaction that leads to
secondary messengers inside the cell being released. So let me draw those. And you've got these secondary
messengers being released, and these are actually
what's stimulating whatever effect is
desired, whether that may be insulin being released
or glucose being taken up inside the cell, or any of
the other countless things taking place in our bodies that
are controlled by hormones. And so in order to give you a
visual for how this might take place in the cell, I've
pre-drawn some pictures in the key. So let me pull those in here. And I want you to be sure
that these drawings are not to scale in any way. But really, this is the
best I can at least do in explaining the process,
because all of this is happening at
the atomic level, and atoms are really tiny. But anyway, what we have in
this picture is a receptor. And I've drawn that
in pink, and it's located inside
the cell membrane. So this is the phospholipid
bilayer of the cell membrane, and we've got the inside of
the cell, and the outside. And then also in
the cell membrane, we've got a G protein, and
I've drawn that in green. It's called a G
protein because it binds to molecules that
include the nucleotide guanine. And that's the same
G from the DNA bases that you might be a little
bit more familiar with. But it's currently
bound to a molecule called guanine diphosphate. And then we'll see
how that changes. But we also have this
adenylate cyclase enzyme that's in the cell membrane. And remember that an
enzyme speeds up reaction. So we're going to see how
adenlyate cyclase speeds up a reaction. But what starts this
process off is the hormone is going to bind
to the receptor. So it's going to look like that. And you're going to have the
hormone bound to the receptor. And once that hormone
binds to the receptor, it's going to change shape. And that's going to allow it
to interact with the G protein here. And so that looks like this. And what you saw happen was
that as the G protein interacts with the receptor in
a hormone complex, it's going to exchange that
GDP that it started with, that guanine
diphosphate for GTP. So essentially, it's
exchanging a guanine bound to two phosphates
for a guanine bound to three phosphates. And what happens is that
enables the G protein to move through
the cell membrane and interact with
adenylate cyclase. And so that activates
the adenylate cyclase. And as an enzyme, that
activated adenylate cyclase facilitates the
conversion of ATP, which is the energy currency
of the cell, into cAMP. And cAMP stands for cyclic
adenosine monophosphate. So we've taken this ATP,
or adenosine triphosphate, and created a cyclic
adenosine monophosphate. And we also have the
additional two phosphates. But it is this
cAMP molecule that activates the protein inside
the cell whose effect is really being targeted by the
hormone in the first place. And so eventually,
this system resets, but not before several
adenlyate cyclase enzymes were activated, resulting in
a lot of cAMP being produced. And so we call this
signal amplification. And what I mean by
signal amplification is that, in theory, one
hormone can bind to a receptor. And that process can
set off a chain reaction that leads to a lot of
cAMP being produced. And so it can mean that
less hormone is required to ultimately activate the
protein or the effect that's being desired. And so secondary
messengers are a means in which hormones
act on the cell. But really, if I'm being
honest, this effect happens differently
for a lot of cells. And all of the mechanisms of
secondary messenger hormone action aren't known right now. And honestly, there are a
lot of secondary messengers other than cAMP. But really, the takeaway
is that for the majority of the hormones in your
body, binding to the cell surface activates a
series of reactions that initiate a response
inside the cell. And so it's very similar to
the use of a phone service provider. And because we as
people-- let me draw us-- because we're unable
to communicate directly with people sometimes, because
of separation or convenience or lack of efficiency,
we use a phone service to project our voice to them
through a phone conversation. So through a phone
conversation, we'll direct our voice to people that
we want to communicate with. Or maybe we use the
delivery of a text message. A text message will transmit
some intended message that we have for people that
we can't communicate directly with, for whatever reason. And so that's very similar to
how secondary messengers assist hormones that can't communicate
with a receptor directly inside of the cell. And so peptide hormones and
catecholamines, both of which can't cross the cell membrane,
use secondary messengers to communicate. And then the other major method
of hormone action on a cell is as a primary messenger. Certain hormones, like
steroids and thyroid hormones, can actually cross
the cell membrane. And it eliminates this
entire middleman system that we set up before. So let me pull in
another cell membrane. And so the hormone
crosses the cell membrane and it binds to
a receptor that's located either in the
cytosol or in the nucleus. And so we could
imagine a nucleus, and there might be DNA inside. But when the hormone binds
to the receptor that's either in the cytoplasm
or inside the nucleus, that binding process is going
to directly affect transcription in the nucleus, or
translation in the cytoplasm, of the protein that's being
activated by the hormone. And this process has quite
a few less moving parts than the secondary
messenger system did. But again, it stems
back to the fact that these are steroid
and thyroid hormones that are typically lipid-based
and are capable of crossing through the cell
membrane on their own. And so they don't need all of
that extra machinery set up for them. But anyway, these are
both primary messengers and secondary messengers. And those are the
two main processes by which hormones
act on the cell that they're created to target.