Biology: Endocrine Cntrl, Signal-Transduction Path

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Have I ever mentioned that the idea to homeostasis is the fact that we have to have inter-organ communication? If that means that organs are going to communicate with other, doesn't that mean that cells need to communicate with each other? And, therefore, homeostasis literally depends on communication in between cells. Now how do cells communicate?
I want to talk to you about how cells communicate because we're going to see that some of the regulatory systems, like, say, the Endocrine system, the system that makes these things called hormones, literally secretes chemicals into your blood and targets them at a given organ, and that's an interesting concept. So, how do signals work? It depends. For example, one signal can have three different responses, depending on the target. I'll give you one. A secretion called acetylcholine. Now, acetylcholine is produced by a variety of body parts, neurons, nerve cells, being one of them, and it depends what it's targeting. So for example, if the acetylcholine lands on a skeletal muscle, in other words, say an arm muscle or one of the involuntary or one of the voluntary muscles, it'll cause contractions. So, in other words, its target is a skeletal muscle, "Boom, muscle contract," and it does. On the other hand, if it's heart muscle, cardiac muscle, it has just the opposite effect. It causes relaxation. An if it happens to be targeting an endocrine cell, one of the hormone producing glands, it causes secretion. Now, that's very bizarre, isn't it? Not really. Because of the point of the matter is, that each of these cells is structurally different and therefore functionally different. The acetylcholine is just acetylcholine. So, the point here is that all of three of these will be targets for acetylcholine, yet all three will react differently because of the way they are by nature.
I want to tell you about a process that is really used a lot in signaling between cells and the way hormones may signal a cell to do a certain job, and that is called a signal transduction pathway. Now, as an introduction to that, let's take a look at two ways a chemical may signal a cell. Remember what we need to do. We need to get a signal to a cell and then into the cell. And if the cell is going to be an endocrine cell, it means that the endocrine cell has to be triggered to make something. Or, if it happens to be a cell being signaled by an endocrine cell, it may be told to make something also. So, there's all sorts of things. There are endocrine cells that send signals. There are endocrine cells that get signals. Endocrine cells - this whole endocrine system, the glands that make your hormones, becomes a very complex scene. For example, here's one thing that can happen. One thing that can happen is that you can have a secretion from a cell, say, an endocrine cell, and it will land on a protein that is on a cell membrane, and that will start a message into the nucleus of the cell. That's one way. On the other hand, the signal may pass right through the cell membrane and signal something inside to signal the nucleus. You think that's simple? Well, it's not. Because there are a lot of different ways this can happen.
Let me give you an example of how this might work. Steroids. Why do I pick steroids? I pick steroids because they are the simplest. Do you know what steroids are? Steroids are called steroids because they are not water-soluble. In other words they are soluble in fats. They are fat-soluble, and some of the things that were steroids, or were considered steroids were things like testosterone and any of those hormones that are going to be able to dissolve in a lipid. And how does that work? How does it transduce a signal? Let's take a look. Here's a good example of a steroid working. Now, since a steroid is fat-soluble, it can pass directly - and here's our steroid - it can pass directly through the cell membrane. Now, the steroids' signal may be "I want the nucleus to start making some proteins." "That's my job." This particular steroid's job. You're going to get in there and you're going to start making proteins. Whatever those proteins might be. It might be, mitotic control factors, it could be anything. So this steroid has to somehow get to the DNA and tell it to work. But since steroids can pass through cell membranes, it's very easy. They can simply diffuse through the cell membrane and bond to a protein. And then that protein steroid complex can go through a Nuclepore and act literally as a regulator on the DNA. So it may come on to the DNA and be a transcription regulator and actually turn on a gene to start transcribing an mRNA that will make a protein. So a fat-soluble protein or messenger is pretty simple to work with. We get a little more complicated though, when we get into some other things. Let me give you an example of non-steroid types of signals. Now it gets much more complex. I'll give you just a couple of examples. First, let me get generic, and then we'll give you a specific example. In a cell membrane of a nonsteroid system, there are these special proteins and these proteins are called G protein linked receptors. What do G protein linked receptors do? They receive, and they're in the cell membrane. And so they may be sitting here and here's a cell membrane and they may be sitting here, just kind of like this, right through the cell membrane. And they're linked to a protein called the G protein, but linked in terms of area. So a G protein might be over here. Now, I've got to tell you about that G protein. The G protein is usually hooked to a chemical called guanine diphosphate - GDP. When a signal comes in, a message comes in, here's what generically will happen. What will happen is this signal will come in there, it will bond to this and then what's going to happen is the G protein is going to exchange GDP for GTP, and then we'll get an interaction here. And then what can happen is another enzyme called adenylate cyclase can get into the mix. Adenylate cyclase is a very important protein because what that will do is that will take a molecule of something called ATP and cause it to form AMP and guess what? Now we come to the whole thing. The transduction. AMP will carry the message. It's the presence of AMP that says, "Okay, the green thing just hit up here, let's do whatever we're supposed to do." So the AMP will carry the message to the nucleus or to another protein to another protein to another protein to another protein, and we call AMP the second messenger. That's what we call that. That's the second messenger.
Let me give you a good example. One example of how this might work. I'm going to use a hormone called epinephrine. You guys probably know epinephrine is something called adrenaline, and what that does is, one of it's ultimate goals is to go the glycogen - remember that animal starch? - and release glucose from it. That's our goal. So, I'm going to go to a liver cell now. That's where the glycogen is, or a muscle cell. I'm going to release glucose. Hang on. Watch what happens here. Watch how it transduces and amplifies the signal. This is amazing. So, in comes the epinephrine, that's step 1, and it's going to go to a G-linked receptor. And going to the G-linked receptor, how many molecules are there? One. Just one. I'm going to try to keep track of numbers here, you're going to love this. Now we get to the whole transduction pathway. So now we've received the message, let's transduce the message.
Here's what's going to happen. The second thing that's going to happen is the G-linked receptor is fine, but now we're going to activate some G's. Some of those G proteins. So we're going to activate G proteins in the way that I just showed you about two or three minutes ago. So we're going to have inactivated G's and they're going to get activated. How many of these are going to happen? Well, because of the idea of them being in the vicinity, this will activate approximately one hundred of these G proteins. Then the activated G protein is going to do something else. It's going to activate the adenyl cyclase. So the G protein will active adenyl cyclase. Well, one to one hundred. Well, then the adenyl cyclase, now that it's activated, what's that going to do? That's going to take ATP and convert it to AMP, the second messenger. And by the way, this is called cyclic AMP because of the way it is formed. Cyclic AMP. We can actually activate 10,000 of these from this hundred. Now each cyclic AMP is going to activate a protein kinase.
Now this is important because protein kinases are phosphorylating enzymes. Remember those? And so we're going to start phosphorylating things. And what are we going to do? We're going to activate a hundred thousand of these. And what's that going to do? The phosphorylate kinase, each one of those is going to activate glycogen phosphorylase. How may? A million of those, and each one of these phosphorylase is going to chop off one glucose molecule. Actually, it's one GP, one glucose with a phosphate hooked on. Look what you've done. You've gone from step to step to step to step to step to step. And what have you done? By taking in this one message of epinephrine, you've been able to chop off one glucose molecule, using each one of these things. That's a signal transduction pathway. And each one of these - so you're going to get a whole lot of glucose molecules chopped off by each one of these things, simply because you hit it with epinephrine. How's that for multiplication?
Animal Systems and Homeostasis
The Endocrine System
Human Regulation: Endocrine Control and Signal-Transduction Pathways Page [1 of 2]