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Cellular mechanism of hormone action

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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.

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  • leafers sapling style avatar for user Can Deva
    this may sound really dumb but what happens to the excessive amount of cAMP that stays in the cell?
    (15 votes)
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  • piceratops ultimate style avatar for user Professor Khan
    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)
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    • leafers seedling style avatar for user Darpan Raghav
      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)
  • piceratops sapling style avatar for user Orlando Leal
    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)
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  • orange juice squid orange style avatar for user litsareth
    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?
    (4 votes)
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    • leaf blue style avatar for user armando.gallegos2
      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.
      (6 votes)
  • male robot hal style avatar for user Brett Kramer
    So can some thyroid and steroid hormones cross the cell membrane but not the nuclear membrane?
    (3 votes)
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    • piceratops seedling style avatar for user Simon Lee
      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)
  • male robot hal style avatar for user Michael Natal
    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)
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  • leafers tree style avatar for user Jocelyn
    why are water-soluble hormones consider as fast-acting than lipid-soluble hormones?
    (0 votes)
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    • leafers seed style avatar for user PCMSIII
      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)
  • piceratops sapling style avatar for user Ryan Fredette
    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)
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    • leaf green style avatar for user Joanne
      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)
  • starky sapling style avatar for user Toby Johnson
    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)
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  • blobby green style avatar for user dcampbell_20
    what is the importance of an intracellular receptor?
    (2 votes)
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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.