12. Endocrinology

Transcription for the video titled "12. Endocrinology".


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Intro (00:00)

Stanford University. Can you give me a little bit of this? Is this better? Yeah. Okay, great. So, yeah, so like Tom said, feel free to ink one sort of ear up as a request. Just raise your hand, do something confusing. Something that I also just like to do. I'm not sure you still have your email.

Overview And Fundamentals Of Endocrinology

Also after class or emails from coursework. You can find the staff back here. So, today we're going to provide a little bit of background context. It produces sort of quick and you're in this kind of place in the context of the other sort of buckets of this class. Or I guess sort of think about it generally. We're going to talk specifically then about peptide and steroid hormones, different types of hormones. Then we're going to see some specific interesting things about them. I want to know. Then we're going to talk about how the brain controls hormones. So, hormone release and eventually feeding back to how hormones influence the brain. Sort of this dual communication system that's pretty neat. We're going to touch on all those things today.

Background Context (01:03)

So, Tom is going to start out with some background context. Okay, so way back when, when life first arose, things were inside single cells, right? Individuals were single cells who had to interact with their environment. They had to get food, they had to give it a waste. They had to make sure they were in the right ph and temperature so that they could do well for themselves. And as a single cell, that seems like a simple enough task. But as things got more complicated and multicellular life arose, there arose a really big important issue for life, which is how cells talk to each other. Cellular communication. Okay? And you don't have to worry too much about like the jargony words at Parachran. But it's kind of worth thinking about. There are four main ways that cells can talk to each other. The first one being cell-cell contact, where you actually have one cell physically touching another cell. And that seems pretty understandable. It's got to be really, really short range. And it's just going to be this cell talking to another cell. We've got Parachran, which is a little more short range. And you guys have heard about neuronal and endocrine. And I'm going to try to put these examples of communication in the context of us as a giant multicellular organism. This class right now, okay? So who wants to be the pancreas? No one wants to be the pancreas. Okay, we've got a pancreas right there. Thank you very much. No, we don't have to be specialized cells. But the point is that a cell-cell contact in our organism would be actually someone physically handing you a note during class. Okay? And it's just one-to-one, short and easy. Not a lot of people are going to know about that signal. Parachran is more like kind of you whispering to a bunch of neighbors, right? A couple people can hear you. It happens pretty quick, but it's not widespread. Nironal is something that is really important to this class, and it's something you've heard about already. This is the equivalent of texting your friend during class, okay? I saw Bill Laundy texting someone earlier. I was a little offended. So you can put your phone away, sir. That'd be great. So, and the key to neuronal transmission is that it's really about electrical movement. Okay? That's why it happens so fast, because I've got neurons that span all the way from here to through my spinal cord, or from all the way from my spinal cord out to the tips of my fingers. Okay? And that's just electrical transmission via action potentials, which you've learned a lot about. Now, granted, when one neuron talks to the next neuron, it's kind of a relay. It's got to use a neurotransmitter to communicate that, but you can really focus for the purposes of this example on that fast electrical action potential thing, and the fact that it's a lot more specific than what we're about to see, which is endocrine, which is long range. It's all about chemical messengers traveling through the bloodstream, okay? Hormones in the blood. That's what endocrine signals are about. This is a lot more like Steven sending you guys an email to the entire class, but it takes a long time to get there, right? It's going to take a little bit longer, but it's going to enable us as a class to coordinate our behavior. So, we all show up to the right place at the right time, wearing the right thing, whatever. Okay. So, you guys, get that. Questions about those different mechanisms of communication? Okay, so endocrine clearly, the focus of today, things are traveling through the bloodstream. It's going to take a while to get there, but it's going to allow us to coordinate a lot of different things. Now, what would we want to coordinate? Two kind of really exciting things that we can coordinate. One is these giant transformations that occur during life. Things like, you know, metamorphosis of, good, I see some mimicking back there, that's very good. I want everyone to do this with me right now. Metamorphosis. Good. So, basically, you want all the cells in that organism to kind of change in coordination with each other. Same thing for a couple other things we're about to talk about. That's in contrast to, it doesn't have to be an adult organism, it just has to be a functioning organism who is in a certain environment. And in that environment, oh crap, I need to get all my cells on the same page because we've got to address this particular environment. It's a particular environmental thing. So, I'll give you a couple examples. One really great coordinated developmental transformation was the transition from young Harry Potter to Daniel Radcliffe, right? He's in that weird horse play thing, got a lot of publicity. And you can see, like, a lot of his cells had to change kind of all at the same time and you get the point. Same thing, I've kind of mentioned these, as opposed to a kind of coordinated response into a specific environmental thing, which might be a stressful situation. We're going to hear about that a little bit later. You want to make sure all your organs and cells are doing the right thing for stress mode or sexual arousal mode, whatever it is. We're going to hear a little bit more about that later. So, who will have some mic? Alright, so that's sort of the background context, putting that stuff into play for today. So, some very important things you have to know about hormones overall. We wrote here, peptide versus steroid. There's technically a third kind of hormone, which is single amino acid, dry hormones. But we're basically going to talk about the distinction between peptide and steroid hormones today.

Peptide versus Steroid (06:42)

And sort of structural differences and what that means in terms of their transport in the bloodstream, the effects they have on target cells. And then we'll see different things about their duration and other cool things like that. So, structure generally. As you can see here, we put up a picture of insulin in peptide form. We want it to make it look like a protein peptides, of course, amino acid being precursors proteins. We see sort of here, this is a typical peptide hormone made from amino acid precursors. And a key term associated with this is the notion that it's hydrofilic. So, this idea that it's water loving. This places to do sort of transform mechanisms involved with it and other things, which we'll talk about in a moment. So, peptide hormones made from amino acids, hydrofilic, water loving. We'll see some examples. You've heard of some already. Insulin, vasopressin, oxytocin, ACTH, CRH, and more. And then we also steroid hormones. So, these are made from cholesterol precursors. They're hydrophobic, water-hating. Another term we associate with this is lipophilic, lightening of lipids. When we talk about the cellular member being made of a phospholipid bilayer, steroid hormones are hydrophobic or lipophilic. They're able to pass through this phospholipid bilayer. It ends up being very important for their mechanism inside of target cells. So, some examples of this. Classic example of glucocorticoids. We're going to see those all over the place. We already have talks about them a bit. Androgens, estrogen, things like that. Something really interesting about the structure of the hormones. So, if we take a steroid hormone, okay. So, I'm not a good wrestler. I'm going to draw a single amino acid, which this actually is nothing like a single amino acid hormone, but you sort of barely think pretend you're... So, a lot of these hormones, steroid hormones, single amino acid hormones, peptide hormones, they home from similar precursors, right? They've peptide hormones, it's amino acids. And single amino acids, it's often from tyrosine, and steroid hormones, it's from these cholesterol precursorsors. Why is this interesting? It's interesting because when they come from the same precursor, they end up looking very similar. So, one might have this here, so this might be one hormone, and then we might have an identical... a new reaction to one underneath, but now it has just another sum of chemical shifts. Chemical structure doesn't really matter. The point is that if you're familiar with some organic chemistry, you have to sum of chemical shifts leading to different hormones. Interestingly, from an evolutionary standpoint, this suggests the need for basically having receptors specialized for these subtle chemical differences in the hormones. Nor if an effort in dopamine have just a slight difference like this, right? But the effect, if the receptor wasn't able to distinguish those between those, it would have a drastic effect. So, it's very important from an evolutionary standpoint to have receptors that can distinguish these subtle differences in the hormone chemical structure. That sounded really technical. Any questions on that sort of general idea? Is that cool? Okay. That does remind me of one thing that I didn't make a distinction between when I was talking about neuronal versus hormonal transport. A lot of times we will kind of throw out these words, and there's a lot of jargony words, norapurnefin baba bah, and it's kind of good in your mind to be able to separate between hormones, things that are really these classic things that travel through the blood of signals and neurotransmitters, right? Neurotransmitters being, they're also chemicals, and they also need to communicate cell to cell, but they are going to be just in that synapse. Okay? From one neuron to the next, in the synapse that you've already heard about, and just to make your guys' lives awesome, there's can be overlap. There can be neurons that release their neurotransmitter into the blood, at which point they become hormones. So, things like dopamine and epinephrine, right? Things you might associate with, neurotransmitters can also be hormones depending on, you know, what context and all that stuff. So, there's something to really focus your attention on when you're distinguishing these signals. Okay, cool. Thanks. So, yeah. So, we talked about the structure very briefly. From that structure we talked about sort of differences in transport. We talked about hydrophobic versus hydrophilic. The images should have done an animation stop pop-up. So, our peptide hormones are going to be water-soluble. They're going to travel freely through the bloodstream. We have, I guess our example here is people riding a roller coaster. These monks are just riding free, looking good. You can imagine the monks are sort of examples of these peptide hormones traveling freely to dissolve through the bloodstream. I really don't dissolve, but that's okay. So, peptide hormones traveling freely through the bloodstream. Steroid hormones, however, they're not water-soluble, so they need to be bound to a chaperone. This is our example of a chaperone guiding this hormone through the bloodstream. So, this is just sort of an interesting thing to note about their transport.

Cell interactions, structure (11:40)

We may talk about this a little later in other contexts. Other interesting things we can learn from the structure. So, interaction with the party cell. When Tom was talking about the context here, it's really important that we understand how hormones interact with cells, right? They require a specific receptor for each individual hormone. We talked about the importance sort of the specificity of that. Peptide hormones and steroid hormones sort of have generalized mechanisms that we're going to talk about, ways in which they interact with the part itself. Peptide hormones on the left here. So, peptide hormones, because they can travel freely through the bloodstream, or I'm sorry, they can travel freely through the bloodstream because of their structural properties. However, those same structural properties, the fact that their hydro-philic prevents them from being able to travel through the phospholipid bilayer of a cellular membrane. So, the receptors for peptide hormones are on the surface of these cells. Their surface receptor, cellular membrane, sort of, the receptors are on the cellular membrane. Because of that, they're typically associated with these who are called secondary messenger responses. The details of this, I think a lot of you guys have been exposed to this in all sorts of biology or human biology. But if you haven't, generally what happens is a peptide hormone binds to the receptor on the cell membrane, and then it sets off what we always call this cascade response, the secondary messenger cascade response. This is actually really interesting. It can lead to a number of different effects. One thing you can do, which we'll talk about when this is a neuron, is you can activate ion channels. Sort of helping ion channels to open or close. We'll talk about that in terms of membrane potential later on. Another thing it can do, and this is the classical example with peptide hormones, is it sets off the secondary messenger cascade. It affects proteins within the cell directly from the cell. So, we can think of peptide hormones generally as having action on proteins within the cell. And that's sort of the end effect of the secondary messenger cascade. They also technically can go into the nucleus and effect transcription. However, that we tend to associate more with steroids. And we'll look at some of the complexities and complications of this later on. You'll hear about this. But I would say generally it's important to note that we tend to associate peptide hormones with the secondary messenger cascade, affecting proteins existing within the cell at the moment. The onset tends to be relatively quick, and the duration is relatively short. We're going to talk about this in comparison to steroid hormones, and we can see why the relative onset duration is different. So, because it's affecting proteins that exist, we can say that the duration is relatively short. And as we said, it may affect protein activity. Stero-d hormones, by contrast, they travel through the blood on these chaperone protein carriers. And then, when they get to a cell, they're able to diffuse through the membrane, and actually bind to receptors located within the cell. Classically, we talk about steroid hormones passing through the membrane, binding to the receptor, and then going directly to the nucleus to effect transcription. So, this is sort of our classic example. Main effect transcription, the onset, then slower, and the duration longer. It takes longer to start these transcriptional processes, processes, and it's lasting a lot longer. So, we're changing the rate of synthesis of proteins rather than changing the proteins that currently exist.

Student questions, cholesterol (15:10)

Okay. As always, feel free to interrupt, if anything seems sort of confusing. So, those are sort of some of the generic examples. We, insulin would be a classic example of peptid hormone, glucuylcortoids, it's our steroid hormone. We may, well, we'll see this coming up again and again. We may touch on this again today in the lecture. So, just to read, does anyone have questions off the bat? Yes? Great question. So, the question was for the receptor, for this in this image, by the way, courtesy of Professor Spolcey, thank you, wherever you are. So, the receptor is located within, the question is where is that receptor located for the steroid hormone? Is it on the nuclear membrane? Is it within the cell? Classically, we're going to talk about basically receptors being located in the cytoplasm. There are examples you'll see if you look, even if you did a Google images search, you might find examples of steroid hormone coming in by the receptor floating in the cytoplasm that's then taken into the nucleus. Basically, we associate the receptors as somewhere within the cell, perhaps on the nuclear membrane, perhaps somewhere else in the cytoplasm, and the steroid hormones bind within there and sort of carry out effects from that. And you can easily also imagine there being a receptor protein that's already sitting on the DNA, just waiting to be activated, and then when the steroid hormone travels the entire way to into the nucleus, that's when it hits the receptor, so yeah, both work. Other questions? Yeah? What is cholesterol made of? So cholesterol -- I have no clue, it's made of. I know generally what its chemical structure looks like. If you look at the steroid hormone picture from the other page, the chemical structure, cholesterol prehearsers are sort of similar, bringing structures, you can look it up. I think it's an interesting question. In my mind, what I tend to associate as a relevant question or something that I'm trying to get across more would be the steroid hormones come from cholesterol prehearsers, and so I sort of consider that the baseline, rather than trying to think about what cholesterol is made from.

Hydrophobic, hydrophilic (17:19)

Interesting question. Don't know if the top line is. And maybe the most important thing would be that cholesterol is hydrophobic, so if you're going to make stuff from this hydrophobic beginning, it's going to be hydrophobic also. And I just want to make sure people are completely -- those are some really jargony terms. Hydrophobic, hydrophilic, there are a lot of synonyms for those terms that are equally jargony, things like lipophilic and lipophobic. Lipo means lipid, so something that is hydrophobic is lipophilic. If I've heard anyone's brains. Okay, so I just kind of maybe spend some time thinking about those words. You can kind of logic through them pretty easily. You might also hear people use the terms polar versus non-polar. Okay, water is polar. So water loving things, hydrophilic things tend to be polar, and hydrophobic things tend to be non-polar. Don't worry too much about that vocabulary. I just want you to know that there's a lot of different words people might throw around that are essentially getting at the same thing.

Brain control (18:27)

Any other questions about this basic setup so far? No, all right. On to Chapter Two, which is how does the brain control hormone release? We've established that it'd be a good idea to release hormones in response to certain environmental cues. How can we control that? And as this picture shows, there are many, many different sites in our body where we can release hormones from. We've got the pancreas right there. We've got the testes. We've got all these different glands. These are just specialized structures that can just pump this hormone into the bloodstream because that's what hormones are all about. Some that'll come up will definitely be the testes, the ovaries for females. I don't know why they're drawn on the same guy here. Kind of interesting. The pancreas, which is we keep talking about this thing called insulin. That's released from the pancreas and it's going to have something to do with food and sugar and things like that. The thymus is another great little endocrine gland that releases thyroid. The thymus is where endocrine signals are the thymus release. Thymus T cells? I'm not sure those are hormones though. So anyway, thymus is involved in the immune system. We'll ignore that for now. And blah, blah, blah. You guys get the point.

Peripheral endocrine, hypothalamus (20:00)

There are many places throughout our body that secrete hormones and they tend to secrete a certain signal. Now, very excitingly, you'll notice that the brain itself has some endocrine glands in it. The hypothalamus. We've heard this word hypothalamus a few times. The hypothalamus is an endocrine gland, meaning it can secrete things into blood. The pituitary right next to the hypothalamus separated by a little blood, maybe not. The pituitary also can release hormones into the blood. And these other kind of lower down peripheral endocrine glands often are regulated by those big master endocrine glands in the brain. I don't know if you guys have been reading your zebras yet, but I think Russer Sapolsky referred to these as the brain is the master of these witless organs. These guys are just kind of like doing whatever the brain tells them to do. And it's the brain controlling via the hypothalamus and the pituitary is going to be able to control how much testosterone is coming out of those testes. Do you have any sense? The brain controls these peripheral endocrine glands. Let's zoom in on that hypothalamus pituitary situation. We really didn't want to include this picture, but I thought it was hilarious and I can't explain why. Maybe it's the ponytail, I'm not sure. But we're just kind of focusing in on these two different parts. And you'll notice maybe that with something to take away from this picture is simply that the brain is kind of feeding into the hypothalamus, which is feeding into the pituitary. So when we see something, that information is processed in our brain, can tell our hypothalamus, "Oh crap, oh crap, it's stressful, it can tell the pituitary."

Sapolsky, anterior, posterior (22:05)

And we get this, eventually we can tell the rest of our body what to do via hormones. Awesome. Goodbye ponytail lady. Okay, here's another just classic, classic Sapolsky image here that we were able to borrow. And this is zooming in once again on just the hypothalamus and now we're really, really looking at the pituitary. And this is where things are going to kind of hit the fan a little bit, so everyone put your A game on to make some metaphor. Okay, so the pituitary. The pituitary are these two kind of things dangling below the hypothalamus, a lot of weird pictures of them. This one's nice because it clearly divides the anterior pituitary from the posterior pituitary. And we're going to make some really, really important distinctions that hopefully you can grasp from this image. And if you can't let me know. Okay, so first of all, the anterior pituitary secretes hormones. It secretes these things over here. I'll talk about them in a second. The posterior pituitary secretes a different set of hormones. These ones over here. That's one distinction. Another really interesting distinction is how the hypothalamus regulates that secretion. Okay, on the anterior side of things, the hypothalamus being an endocrine gland can actually drop some hormones into that little red river of blood right there. Okay, so the hypothalamus is actually releasing a hormone into the blood and that travels down to the posterior pituitary and tells those cells to then release another hormone into the blood. And once they're in the blood, they can go all the way down to those other target organs we talked about. So that's one system. You've got to actually travel through the blood and the anterior pituitary. The posterior pituitary is actually directly innervated. Okay, so the hormones that are released by the posterior pituitary are actually coming out of those neurons.

Peg. (24:18)

Okay, and the cell bodies of those neurons are up in the hypothalamus. So a couple examples, let's go through the examples. You absolutely do not need to memorize this. We only do this because we'll teach us M-Pak and those kids really like their acronyms. They like things that you can say out and put around and put them in both. The flat peg is the acronym that people use when they want to memorize a lot of stuff to memorize the posterior, sorry, the anterior pituitary hormones. Some that will be relevant to us that you might want to keep in mind are particularly ACTH. Don't worry about it quite yet, but just kind of plug it in your mind to something cool. And a couple of these other ones might come up as well, but whatever. On the posterior side, we were upset because there was no cool acronym. Is that the right word acronym? For the vasopressin and oxytocin, and we decided that since these are the two hormones that are always getting shouted out in these bowl studies, we put some bowls on there. And we thought they were cute. They kind of got some Rudolph things going on with the noses. So yeah, whenever you're hearing about vasopressin and oxytocin, those are hormones that are released from the neurons that go from the hypothalamus to the post-opressin. Now, questions about any of that? That's kind of some neuro-anatomy. You're probably not super excited and interested in about that, but it's useful to know. It might come up a little bit. So questions, clarifications. None at all. Oh, yes.

Vasopressin & oxytocin. (26:17)

Oh my, that's a great question. So I don't know how much we got into kind of -- oh, sorry. My question was the neurotransmitter/chormones, like vasopressin and oxytocin that are released in the posterior pituitary, are those just kind of like sitting there waiting to be released, or do those have to be manufactured and then sent over there? Is that a question? Yeah. If they're released from the other side of the hospital, do you think they're released from the hospital? Are they released when needed, or are they created and then sort of sit there? Okay. So yeah, I would think about this based on your typical understanding of a neuron, which just has a cell body, an axon, and then the axon terminal, which is where it releases neurotransmitter, right? And that axon terminal where it releases neurotransmitter, it's got vesicles. It's basically got these giant balls full of neurotransmitter. Same thing here. You got these giant balls full of octetosin and vasopressin just waiting to be released. Those, like any other neuron, those are synthesized produced in the cell body of that neuron, which exists in the hypothalamus. And if you're interested in how that works, you've got to go on this crazy journey where stuff, proteins, whatever, made in the cell body of that neuron, which you can see up there. Has to be carried by these motor proteins down the cytoskeleton. They walk like this. And they have to walk all the way down the cytoskeleton to get there so that they can just wait for the right signal. That's an excellent question also. Getting at a deeper issue, which is what is it that means you just call it a hormone release, and we're going to cover that in our chapter three coming up. Yeah. So yeah, clearly there are neurons telling the hypothalamus neurons when to be activated, when to release vasopressin. Other questions about this slide? Does anyone totally confuse this to what it is even talking about? Or you guys feel okay? Feel okay. All right. One last thing on this one is I'd like to contrast it to Dana's excellent talk on the autonomic nervous system, okay, where you guys learned a lot about a lot of different things, including the phytoplases. Including the fact that the brain can control the autonomic nervous system, right? And the brain actually sends neurons with their cell bodies in the hypothalamus, and instead of sending them to the pituitary, it sends them some other root down your spinal cord and out. And when we were talking about the autonomic nervous system, and it being also controlled by the hypothalamus, this is just kind of a reminder, okay? The brain and the hypothalamus are really, really important for regulating a lot of things in the case of endocrine systems. This is how it works. Cool. Awesome. Now, we're going to look at just one example of kind of zoom back out from the lady with the ponytail to the zulu, the ovaries and the testes to remember kind of how all this works together. Okay, and I could have done many different systems, right? Because we had all those different peripheral organ, peripheral endocrine glands that needed to leak juice out into the blood. I chose this one because it comes up a lot in the class, and it's often referred to, okay? So it would be the hypothalamic pituitary adrenal axis. The adrenal gland is one of those several glands, okay? It is regulated by whatever hormones are in its environment, okay? And whether that hormone is there is thanks to the pituitary and so forth, okay? There's this kind of cascade of events that allow the brain to control a peripheral gland. And in terms of exactly which hormones do that, we see that the hypothalamus is going to have to leak some CRH into that portal vessel. That we saw for the anterior pituitary, right? So those neurons on the upper left would leak, leak, leak some CRH. I might even choose not to tell you what CRH stands for. And let's just say it's CRH, and then CRH travels through that blood until it gets to those neurons, where it activates ACTH. It activates neurons, sorry, not neurons, it activates endocrine cells to secrete ACTH into the blood, and then that travels through the entire body's bloodstream, okay? So it's going to go all over the place, but it just so happens that the cells that really like to respond to ACTH are in the adrenal gland. So the adrenal cortex is kind of chilling right on top of your kidneys, having a good time. And when ACTH is present, it will release glucocorticoids. That's a big scary word. It's a very important word, okay? Because this is the stress hormones. And for you guys who have started reading zebras, you'll have read a lot about glucocorticoids already. They are going to be a really important hormone throughout the second half of the class. So glucocorticoids, stress hormones, one specific one that often gets referenced is called cortisol, okay? And we don't have to worry about it too much right now. You just remember stress hormones are getting pumped out. So we kind of understand these first two positive arrows, I hope. Brain sends an arrow to the deuterium, sends an arrow to this via hormones. Now, when cortisol comes out, and it travels through the systemic blood circulation, it's kind of knocking on all the doors of every single cell in the body saying like, "I'm going to-- I'm going to-- on cortisol, I'm here to party." And if that cell has a receptor, this is a theme coming up, then it will respond, okay? And some of the cells that have receptors for cortisol are in the pituitary, and some are in the hypothalamus. And what that allows for, it allows the pituitary to know how much cortisol is in the system. So when it kind of realizes, "Oh my God, yay, the ACTH made it there." And cortisol came out, now that I hear the cortisol is the procedure, I'm going to stop. I'm going to slow down on the ACTH, and I'm going to relax a little bit. And that's something called negative feedback, okay? Negative feedback, big term and biology and all this stuff just means that the more cortisol you get it to send out, the less ACTH, okay? It's kind of a balancing mechanism. It brings us back to baseline so that we stop secreting so much down cortisol. Same thing exists, there's a whole other area for negative feedback in the hypothalamus, and I think that in the more advanced endocrine lectures, we'll learn about another site of negative feedback, okay? Other parts of the brain that when they hear cortisol can slow this cascade down. So any questions about negative feedback? What is the HPA axis? Why does it represent everything we're learning? Okay, great, thank Tom. So Tom pointed out my least favorite slide of the day earlier. This happens to be my favorite slide. This is one of those slides where it looks like it's fairly simple, but actually a lot of thought went into this. So much so that we probably spent like two hours with the original slide, scrap that, and then about an hour ago, change it to this. So here it is. Very important question. Stepping from the things that Tom just talked about, this hormone being released and feeding back to the brain, we're going to investigate that a lot more closely now. We're going to look at hormone action on the brain. We're going to talk a lot about the hormone and receptors for hormones. We mentioned very briefly earlier sort of a generic cellular response to having a hormone found to a receptor either on the surface or inside the cell. Now we're going to talk about specifically in the brain. So we have hormone to the neuron, an epic journey. The reason is why we're trying to come up with the perfect analogy for a hormone returning to the brain. Something historically that had to go on an epic journey to deliver a message where there were sort of proper receptors to receive the message. So we thought about sort of sticking with the Harry Potter theme and going with Kingsley Shackle Bolt's control list to go in the first wedding. I was a part of this. But I decided that didn't quite work. We thought about the festivities. The ancient Greek guy who went from marathon to Athens to deliver the message that Greeks defeated the Persians, which is why the marathon is 26 miles. Also didn't work. So we stumbled upon this, which is a picture of a poem of the years. The guy who supposedly said the British are coming. The reason this is such a good example, or at least we can stretch it a bit here, is that a hormone secreted from an endocrine gland. Let's say we're starting sort of from a target organ here. And as you've told me, we just mentioned cortisol coming from this adrenal cortex and going back to the brain. It has to travel through a wholeness, through the bloodstream. Interestingly, in order for cortisol to be screwed in the first place, it received a signal. In this case from ACTH, ACTH binding to receptors stimulating to release a cortisol. Paul Revere was sitting out one night. This is the guy back in 1775. Actually a week ago today, and like 325 years ago or something like that. 70-75, so that map is probably way up, but you can figure it out. He was sitting outside waiting to see these lightbeats. He was waiting to receive a signal. I think the Paul Revere is sort of a group of hormones here. And when the signal came in, these two lightbeats, he set off on this path through the bloodstream, him horseback through the roads, and with this message. And he didn't actually say that a British are coming. He said, "Boy, what was it?" Something like the normals, something like that. I may have foreseen it down. No, I didn't. Okay, well he said some code word. And basically this code word, if there were proper receptors for it, they knew how to respond. So it wasn't just a British component. It was some other word, and if there were receptors for it, they could respond. The relevance in this case is we're talking about going back to the brain. So Paul Revere was going to Lexington, sort of the central hub, this central neural system brain. We could sort of stretch it that way. And has to find the proper receptors there to initiate this proper response. So, I don't know, I just like that analogy. So what we're going to talk about is hormone back to the neuron, has to get through the blood brain barrier. It does the neurons, it's going through the neuron or the group of neurons. Do they have the proper receptors for this hormone signal? And once it binds, how does it influence activity in the brain? What is going on there? Questions so far? Did I confuse significantly with that? Okay, cool. So we're going to move on. Starting with the blood brain barrier. So the blood brain barrier. On the left, we have this picture of just blood vessels in the brain.

Blood-Brain Barrier (37:38)

This is here because Tom, sort of as a personal mission, he and I know what we've been confused about what the blood brain barrier is, what it looks like. He used to envision, you can tell. It's just really embarrassing to say to myself, I used to think that the brain was in this barrier that protected it from the able blood supply. Obviously, it can't be like that because the blood has to get inside the brain and tell every single cell in the brain what to do. And I'm confessing this to you today, that you actually have to picture the blood vessels, access to the brain in a much more complicated way. So the barrier itself is much more complicated. Right, so the barrier is constructed by basically these epithelial cells lining the blood vessels. Right, the blood vessels extend throughout the brain, just sort of an image of it there. And we have this blood brain barrier created by these tight junctions and epithelial cells, sort of a bunch of details that aren't necessary. However, it's interesting because this barrier, this blood brain barrier, basically tightly regulates what type of things can go inside and outside the blood stream in the brain. It's very important that we have a lot of control over what's going on in terms of blood supply in the brain. So hormones, the question comes up, can hormones pass through the blood brain barrier? We do a bunch of research on this and basically because these are epithelial cells, possible lipid bilayer, same story. Steroid hormones are lipophilic, they can pass through this blood. This possible lipid bilayer, not much of a problem there. Peptide hormones, generally we know that they can't pass through just on their own, but we look this up. There doesn't seem to really be a problem with peptide hormones getting to the places they need to get in the brain. Because they have these carrier transports, they have the ability to get through the blood brain barrier when they need to. So just sort of an interesting point there. First step, getting through blood brain barrier, it's helpful to know it exists. It might come up in other contexts later on. Things like alcohol can go right through the blood brain barrier and that has certain effects on behavior. It might come up later on, here's this blood brain barrier, what can get through it, what does that mean, what are the implications for that in terms of behavior. So we just sort of know about generally. So next step, receptors. So hormones, when they're traveling back to the brain, there have to be appropriate receptors for these hormones. Tom talks about cortisol, an example of the glucocorticoid. Glucocorticoid is steroid hormone. This is an image of a rat brain and glucocorticoid receptors in the rat brain. We also have mineral corticoid receptors, which we're not really going to focus on in blue. An example would be like aldosterone for my amputeal, you know what that is, but we'll, thanks for the nod day. But we're not going to focus on that. So glucocorticoid receptors, as you can see, there are glucocorticoid receptors throughout the rat brain. Interestingly, how do we see them sort of clumped in certain areas? What's going on there? This might suggest a particular area that's particularly sensitive to these glucocorticoid hormones. So these glucocorticoid hormones come into the brain, diffuse through the membrane, and bind to these receptors located in the brain. We see here that one area is the hypothalamus. Tom already mentioned one effect of what's going on there, potentially sort of these negative feedback mechanisms. So glucocorticoids coming back and helping to regulate or down-regulate the release, the immune system, basically suppress the release of CRH, and eventually ACTH and other things affecting cortisol's release in the first place. We also see these receptors clumped in the hippocampus here. So another interesting potential, other type of negative feedback thing going on there. Stay tuned. We may hear more about this later on. Interesting point though is that for every single hormone, we're going to have unique receptors throughout the body, but we're looking at the brain right now. So we're going to have unique receptors for these hormones in the brain. We're going to want to be paying attention when we're looking at behaviors. We're going to want to think about basically where are these receptors in the brain, what types of receptors are they, that sort of thing. On the side, we wrote receptors, location type, and how many. So I briefly just talked about location. Location of receptors, how that can matter. Type of receptors. You can have within an individual, you can have different types of dopamine receptors for example. You can have multiple different types of receptors for a particular hormone, and this can lead to different effects depending on what type this is. We also heard about this on sort of the population level, a variation in the type of vasopressin receptor and how that can relate to sort of monogamous versus tournament species type behavior. I guess maybe stay tuned for this, but we've also heard about these things before. So types of receptors are interesting, location of receptors, how many receptors. This is another question that becomes very important. If we have a lot of receptors, we can basically predict that there's going to be a higher sensitivity to the hormone in that area. The low amount of receptors, not as sensitive. When we look at, when we talk about meanies rats, epigenetic mechanisms, just as supposed to be basically affecting the expression of receptors. In certain parts of the brain, and then we can see the behavioral impacts of that. Another thing briefly related to how many receptors we have, we have the level of hormone and we have the level of receptors. Both these things basically impact the behavioral output. The interesting effect we can begin to see happening is that the level of hormone can affect the upper regulation or down regulation of receptors.

Hormone Effects And Receptor Regulation

Receptor Regulation (43:04)

You might start out with a certain amount of receptors, and then if you're flooded with tons and tons of hormone, these receptors then might start to down regulate. The cell might sort of down regulate the amount of receptors expressed on the surface of the cell, and you might see down regulation. Conversely, we might see up regulation if it's not receiving enough of this hormone. Stay tuned for more of this, complexity of this, complications of this, et cetera. Any questions so far on this stuff? Okay, cool. So, hormone action on the brain. Next we turn to basically looking specifically at a neuron. As I mentioned before, we talked about sort of the effects on cells. We talked about peptide hormones in the secondary messenger cascades. We put the image back up, talked about steroid hormones, and generally affecting transcription. Now we basically want to zoom in on a neuron and see what types of effects could be happening on these cells, these brain cells.

Potential Effects of Hormones on Neurons (43:56)

So, we wrote down here, we summarized very nicely, potential effects of hormones on neurons. Once the hormone binds to a receptor, we can have it change the membrane potential via ion channels. So, maybe secondary messenger cascades, if basically some molecule of some sort bumps into another channel, opens it more. Now you've changed the membrane potential of the cell. It either becomes easier or more difficult to start an action potential, something like that. We can change transcription of genes. So, it can go in like we saw this with the steroid hormone going in and basically binding to DNA, affecting transcription of genes. In this case, the genes, they could be receptors. This might be sort of mechanism for upper regulation and down regulation of receptors, something like that. We can also have, of course, changed protein activity in transport. This, of course, is crucial, right? Proteins could be involved with tons of things. Neuro-transmission, formation of new synapses, the things listed there. Basically, hormones can have impacts on all of these different areas. Protein activity, transcription, membrane potential, all these different things. And so, at an individual cellular level, we can begin to see sort of the wider rate of impacts by hormone binding. What that can do? If you step back and think about this as sort of network to neurons, not just individual neurons, but network to neurons. Now you can begin to see how hormones can start to shape behaviors more overall. Just these networks of neurons, these, and those behavioral inputs being sort of the opposite networks. Yeah, question. We talked about impact on neurons, do you mean cells that are in the brain? And the center neurons are sort of talking about the brain. Great. So, question, actually, can you repeat that for me? I would like to call central neurons as just like just the brain. Whole central nervous system or just the brain? So, in this case, I'm talking about neurons that are in the brain, but these might project anywhere. So, in terms of neurons can project to other areas within the brain, can project on a spinal cord and elsewhere. So, the impact could be essentially anywhere that these neurons could project. When we're talking about the effect of hormone input on neurons in the brain, the key is the neurons, right, where they project. They'll have a certain impact on, they'll have some certain output where they project to. But in the first place, they have to have a receptor for this hormone to bind. So, it's just something interesting to note. Other questions? That's not a question. Okay, cool. Good, thanks. So, I think that's kind of summarizes my thing on that. Tom, did you have anything to add to that? I'd say the more interesting things that we're talking about, neurons changing activity. Neurons in the brain is where the interesting stuff is happening. Maybe the lordosis reflex has more of the, you know, how hormones might influence how likely you are to do your little back heart arrays, but who knows? Okay, cool.

Interactions Between Hormones And Nervous System

Hormone-Nervous System Interaction (46:46)

So, yeah, so we talked about the nervous system lectures, how behavior is affected by the nervous system. Now we've talked about how hormones can affect the nervous system and therefore sort of affect behavior as an output there. We're going to be a little preview of some areas we might see hormones interacting in future lectures. So, stress. We're definitely going to see glucocorticoids associated with stress response. Here's Harry and Sirius looking sort of stress. Sexual behavior. testosterone, estrogen, vasopressin, oxytocin. We're going to see these things as players in sexual behavior lectures. Aggression, testosterone, again, glucocorticoids, estrogen, epinephrine. Depression. Okay, I'll just, there's something about that picture. All right, and depression. But depression, glucocorticoids, styrodenormone, estrogen, progesterone, melatonin. Great, so some things. Yeah, just something to add for this slide is we're kind of throwing a bunch of random hormones at you that you might not be familiar with yet. Something to think about is how every single thing we've told you thus far regarding receptors and hormone levels and room for individual variation and all these things, levels where they are, what type of receptors might influence these things. That's going to be kind of how we walk through a lot of these behaviors. Cool. Last slide is just take home points. Things that are really excellent for you to try to walk away with, so don't walk away if you don't understand most of these things. But steroid versus peptide hormones and the importance of what it means to be hydrophobic. Okay? Pretty much a lot of the consequences for how we distinguish between these two things. It depends on whether you're hydrophobic or hydrophilic, so it makes it pretty easy to logic through if you know that basic thing, whether you need the chaperone or not. And how or where your receptor is going to be. The nervous system control of hormone release. You guys, I kind of hit that into the ground, the HPA axis as one example of how the brain could control peripheral endocrine glands. And then finally, when those hormones are released, how can they influence behavior via neurons, kind of the long trials and tribulations of power, polyurever, really excellent analogy, I think. Thank you guys at all agree. And yeah, basically that's it. So if you guys have any questions, you can shout them out or just come down here and ask us because you guys have fun things to do today. Thank you.

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