Stanford University uh can you hear me like this is this better okay great so um yeah so like Tom said Feel Free at any point to sort of interrupt us with questions just raise your hand if something is confusing uh stuff like that also just like with the other lectures feel free to email us after class or emails around coursework um if you find us that way uh so today we're going to provide a little bit of background context introduce sort of quick end an system in place in the context of um the other sort of buckets of this class or or I guess sort of think about it generally uh we're going to talk specifically then about peptide and steroid hormones different types of hormones that we're going to see some specifics um interesting things about them that you might want to know uh then we're going to talk about how the brain controls hormones so hormone release and then eventually feeding back to how hormones influence the brain sort of this dual Communication System that's it's pretty neat um we're going to touch on all those things today so Tom going to start out with some background context okay so way back when when life first arose things was were inside single cells right individuals were single cells who had to interact with their environment they had to get food they had to get rid of 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 Rose 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 like paracrine um 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 um we've got paracrine which is a little more short range um and you guys have heard about neuronal and endocrine um 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 pan okay we got a pancreas right there thank you very much um no we don't have to be specialized cells but the point is that um a cell cell contact in our organism would be actually someone physically handing you a note during class okay you actually and it's just one to one short and easy not going to not a lot of people are going to know about that signal paracrine 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 neuronal 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 ly texting someone earlier I was a little offended so you can put your phone away sir that'd be great um 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 neurot transmitter 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 um 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 be 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 um good I see some mimicking back there that's very good I want everyone to do this with me right now metamorphosis good um 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 which I'm about to talk 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 C on the same page because we've got to address this this 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 to Daniel Radcliffe right he's in that weird horse play thing got a lot of publicity um 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 um 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 will has the mic all right so that's sort of the background context putting that stuff into play for today um so some some very important things you have to know about about hormones overall um we wrote here peptide versus steroid there's technically a third kind of hormone which is single amino acid um Drive hormones uh but we're basically going to talk about the distinction between peptide and steroid hormones today and and sort of structural differences and what that means in terms of their transport um in the bloodstream the effect they have on target cells um and then we'll see different things about their duration and uh other cool things like that so structure generally um as you can see here we put up a picture of uh insulin in peptide form we want it to make it look like a protein peptides of course um amino acids being the precursors to proteins um we see sort of here this is a typical peptide hormone um made from amino acid precursors and a key term associated with this is the notion that it's it's hydr philic so this this idea that it's water loving um this this plays into the uh sort of transport mechanisms involved with it and other things which we'll talk about in a moment so peptide hormones U made from amino acids hydrophilic water loving we'll see some examples you've heard of some already um insulin vas supressant oxytocin act CR and more um and then we also have steroid hormones so these are made from cholesterol precursors uh they're hydrophobic water hating another another term we associate with this is lipophilic um liking of lipids when we talk about the cell cellular membrane being made of a phospholipid bilayer um steroid hormones are hydrophobic or lipophilic they're able to pass through this FX toin bilayer ends up being very important for their mechanism inside target cells uh so and some examples of this classic example glucocorticoids we're going to see those all over the place we already have talked about them a bit um androgens estrogen uh things like that something really interesting about the structure of the hormones um so if we take a steroid hormone uh okay so I'm not going to draw steroid I'm going to draw a uh single amino acid which this actually is nothing looks nothing like a single amino acid uh hormone but you sort of bear with me and pretend here so um a lot of these hormones steroid hormones uh single amino acid hormones peptide hormones they come from similar creatur right in peptide hormones it's amino acids and single amino acids it's often from tyrosine and steroid hormones it's from these cholesterol precs precursors 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 nearly identical one underneath but now it has just another subtle chemical shift chemical structure doesn't really matter the point is that if you're familiar with some organic chemistry you have just subtle chemical shifts leading to different hormones interestingly from an evolutionary standpoint this suggests the need for uh basically having receptors specialize for these these subtle chemical differences in the hormones um norrine and dopamine have just a slight difference like this right but the the the effect if the receptor wasn't able to distinguish those between this it would have a drastic effect so it's it's very important from an evolutionary standpoint to have receptors that distinguish these these subtle differences in the hormon chemical structure um 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 um uh make a distinction between when I was talking about neuronal versus hormonal transport okay A lot of times we will kind of throw out these words and there's a lot of jargony words Norine blah blah blah and um 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 cellto 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 just something to really focus your attention on when you're distinguishing these signals okay cool thanks so yeah so we talk about the structure very briefly um from that structure we can talk about sort of differences in transport we talked about uh hydrophobic versus hydrophilic uh the images should have done an animation style pop up so our peptide hormones are going to be water soluble they're going to travel freely through the bloodstream we have uh I guess our example here is people riding a roller coaster uh these monks are just riding free uh looking good uh you can imagine amongst the sort of examples of these uh peptide hormones traveling freely dissolved through the bloodstream not really dissolved but that's okay so uh peptide hormones traveling freely through the bloodstream steroid hormones however uh they're not water soluble so they they need to be bound to a chaperon this is our example of a chaperon uh guiding this hormone through the bloodstream so um this is It's just sort of a an interesting thing to note about their transport uh we may talk about this a little later um in other contexts other interesting things we can learn from the structure so interaction with the target cell um 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 for each individual hormone we talked about the importance sort of 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 they interact with target cells peptide hormones on the left here uh so peptide hormones because they they can travel freely through the bloodstream um or I'm sorry let me step back they can travel freely through the bloodstream because of their structural properties however those same structural properties the fact that their hydrophilic 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 uh cellular membrane sort of The receptors are on the cellular membrane um because of that they're typically associated with these what are called secondary messenger responses uh the details of this I think a lot of you guys have been exposed to this in in all sorts of biology or human biology but if you haven't generally what happens is a peptide hormone binds to a receptor on the the cell membrane and then head off what we always call this Cascade response the secondary messenger Cascade response this is actually really interesting um it can lead to a number of different effects uh one thing it can do which we'll talk about when when this is a neuron is it can activate ion channels um 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 it sets up the secondary messenger Cascade that affects proteins within the cell directly within the cell so we can think of peptide hormones generally as having action on proteins within the cell um and that's sort of the end effect of the secondary messenger Cascade they also technically can go into the nucleus and affect transcription however that we tend to associate more with steroids uh and we'll look at some of the complexities and complications of this later on you'll hear about this um but I would say generally it's it's important to note that we tend to associate peptide hormones with these secondary messenger Cascades affecting proteins um exist within the cell at the moment uh 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 the relative onset duration is different um so because it's affecting proton or proteins that exist it's we can say that the the duration is is relatively short and as we said here may affect protein activity steroid hormones by contrast they travel through the blood on these chaperone um protein carriers and then when they get to a cell they're able to diffuse through the the membrane and actually bind to receptors located within the cell classically we talk about steroid hormones passing through the membrane binding to a receptor and then going directly to the nucleus to affect transcription so um this is sort of our classic example main effect transcription uh the onset then slower and the duration longer um it takes longer to start these transcriptional processes process use and it's it's lasting a lot longer which changing the rate of synthesis of proteins rather than changing the proteins that currently exist okay as always feel free to interrupt if anything seems sort of confusing so um th those are sort of some of the generic examples uh we insulin would be a classic example of peptide hormone glucocorticoids is our steroid hormone um we may we we'll see this coming up again and again we may touch on this again today in the lecture cool so just to rec B does anyone have questions off the bat yes um for the steroid it's aor floating in the middle of cell like would that be like on Nu envelope or is it something else great question so the question was for the receptor for this in this image by the way courtesy of Professor spolski uh thank you wherever you are um so uh 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 um classically we're going to talk about basically receptors being located in the cytoplasm there are examples you'll see if you look um even if you did a Google Images search you might find examples of steroid hormone coming in binding a 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 and sort of carry out effects from that and you could 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 are chol what what is cholesterol made of uh so cholesterol uh I have no clue what it's made of I I know generally what its chemical structure looks like if you look at the steroid um hormone picture from the other page the chemical structure uh cholesterol precursors are sort of similar ring structures you can look it up um I think it's an interesting question uh in my mind what I tend to associate as as a a relevant question or or something that I'm trying to get across more would be that the steroid hormones come from cholesterol precursors and so I sort of consider that the Baseline rather than trying to think about what cholesterol is made from interesting question don't know off the top of my head 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 um and I just wanted 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 right lipo means lipid so something that is hydrophobic is lipophilic that hurt anyone's brains okay um so just kind of maybe spend some time thinking about those words you can kind of logic through them pretty easily um you might also hear people use the terms polar versus nonpolar okay water is polar um so water loving things hydrophilic things tend to be polar and hydrophobic things set to be nonpolar 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 all essentially are getting at the same thing 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 um how do how how can we control that um and as this picture shows um there are many many different sites in our body where we can release hormones from um we've got the pancreas right there we've got the testes we've got all these different different glands okay these are just specialized structures that can just pump this hormone into the bloodstream because that's what hormones are all about um 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 um the pancreas um 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 um the thymus is another great little endocrine gland it releases um thyroid no thymus release oh thymus is where what what what uh endocrine signal does the thymus release thymus te- cells I'm not sure those are hormones though so anyway thymus is involved in the immune system Let's ignore that for now um and blah blah blah you guys get the point there are many places throughout our body that secrete hormones and they tend to secrete a certain signal um now very excitingly you'll notice that the brain itself has some endocrine glands in it okay 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 hypothal is separated by a little blood maybe maybe not um the pituitary also can release hormones into the blood okay and these other kind of lower down peripheral endocrine glands um often are regulated by those big Master endocrine glands in the brain okay I don't know if you guys have been reading your zebras yet but he but I think Professor spolski referred to these as uh oh the brain is the master of these witless organs okay these guys are just kind of like doing whatever the brain tells them to do and it's the brain that controlling via the hypothalamus and the pituitary is going to be able to control how much testosterone is coming out of those testies okay do that make sense the brain controls these peripheral endocrine glands okay so let's zoom in on that hypothalamus pituitary um situation will really didn't want to include this picture but I thought it was hilarious and I can't explain why um maybe it's the ponytail I'm not sure um but we're just kind of focusing in on these two different parts um and you'll notice maybe that with with um 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 we when we when we see something right that information's processed in our brain can tell our hypothalamus oh crap oh crap it's stressful it can tell a pituitary and get this eventually we can tell the rest of our body what to do via hormones awesome goodbye ponytail lady um okay here's another just classic classic sauli image here that we we were able to borrow um 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 I want everyone to put your put your aame on to mix a metaphor okay um 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 um 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 first all 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 the how the hypothalamus regulates that secretion okay on the anterior side of things the hypothalamus being an endocrine gland can actually drop some hormone 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 sorry the anterior pituitary sorry um 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 got to actually travel through the blood in the anterior pituitary the posterior pituitary is actually directly inated okay so the hormones that are released by the posterior pituitary are actually coming out of those neurons 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 did this CU will teaches MCAT and those kids really like their acronyms they like things that that you know you can say out and put around and put them in bold so flat Peg is the acronym um that people use when they want to memorize a lot of stuff to memorize the posterior or sorry the anterior pituitary hormones some that will be relevant to us that you might want to keep in mind are particularly um act okay don't worry about it quite yet but just kind of plug it in your gr is something cool um and a couple of these other ones might come up as well but whatever on the posterior side we 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 V studies we put some vs on there and we thought they were cute they kind of got some Rudolph things going on with the noses um so yeah whenever you're hearing about vasopressin and oxytocin those are hormones that are released from the neurons in that are go from the hypothalamus to the posterior pituitary now questions about any of that that's kind of some neuroanatomy you're probably not super excited and interested in about that but it's it's useful to know it might come up a little bit so questions clarifications none at all there oh yeah yes oh my that's a great question um so I don't know how much we got into kind of oh sorry the question was the the neurotransmitter slh hormones 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 the question yeah like if they're Rel are they released when needed or are they like created and then sort of sit there okay so yeah I would think about this um based on your typical understanding of a neuron which just has a cell body and axon and then the axon terminal which is where it releases neurotransmitter right and in that axon terminal where it releases neurotransmitter it's got um vesicles it's basically got these giant balls full of neurotransmitter same thing here you got these giant balls full of oxytocin 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 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 I'm serious I'm um and they have to walk all the way down the side of skeleton to get there so that they can just wait for the right signal that's that's an excellent question also there getting at a deeper issue which is what is it that leads to give this hormone release and we are going to cover that in our our chapter three coming out yeah yeah so yeah clearly there are neurons telling the hypothalamus neurons when to be activated when to release fast oppressing other questions about this slide that's is anyone totally confused as to what it is even talking about or you guys feel okay feel okay um 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 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 important for regulating a lot of things in the case of endocrine systems this is how it works cool um 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 dude with the ovaries and the testes to remember kind of how all this works together okay and I could have done many different systems right cuz 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 um 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 those neurons on the upper left would leak leak leak some crh I might even choose not to tell you what CR stands for um and let's just say it's CR and then CR travels through that blood until it gets to those neurons where it activates act um okay it activates neurons or sorry not neurons it activates Endocrine cells to secrete act 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 act are in the adrenal gland so the adrenal cortex um it's kind of chilling right on top of your kidneys having a good time and when Act is present it will release glucocorticoids now that's a big scary word it's a very important word okay because it's invol this this is the stress hormones and for those 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 just remember stress hormones are getting pumped out um so we kind of understand these first two positive arrows I hope brain sends an arrow to the pituitary 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 y I'm going to I'm cortisol I'm here to party um 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 when it when it kind of realizes oh my God yay the Act made it there and cortisol came out now that I hear the cortisol as the I'm going to stop I'm going to slow down on the ACT and I'm going to relax a little bit and that's something called negative feedback Okay negative feedback big term in biology and all this stuff just means that the more cortisol you get it to send out the less act okay it's kind of a balancing mechanism brings us back to Baseline so that we stop secreting so much dang cortisol same thing exists there's a whole another 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 okay great thank Tom so Tom uh pointed out my least favorite slide of the day earlier this happens to be my favorite slide uh this is one of those slides where uh it looks like it's it's fairly simple but actually a lot of thought went into this uh 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 uh important very important question um stemming from the things that Tom just talked about these 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 um we're going to talk a lot about the the hormone and receptors for hormones uh we mentioned very briefly earlier sort of a generic cellular response to having a hormone bind to a receptor either on the surface or inside the cell now we're going to talk about um specifically in the brain so we have uh hormon hormone to the neuron an Epic Journey uh the reason this slide took so much work is we were trying to come up with the perfect analogy for a hormone returning to the brain uh something historically that had to go on an epic journey to deliver a message uh where there were sort of proper receptors to receive the message uh so we we thought about sort of sticking with the Harry Potter theme and going with uh Kingsley shackle bolts Patronis to bill the fl's wedding at Tom was par IDE uh but I I decided that that didn't quite didn't quite work uh we thought about fifties uh the the ancient Greek guy who went from uh Marathon to uh Athens to deliver the message that Greeks had defeated the Persians which is like the route or why the marathon is 26 mil also didn't work uh so we we stumbled upon this which is uh a picture of Paul Riv uh the guy who supposedly said the British are coming um the reason this is such a good example well or or at least we can stretch it to fit here is it um a hormone secreted from from an endocrine gland let's say we're starting sort of from a Target organ here uh and and we Tom just mentioned cortisol coming from this adrenal cortex and going back to the brain um it has to travel sort through a hormone has to travel through the bloodstream uh interestingly in order for cortisol to be secreted in the first place it received the signal right in this case from act act finding to receptors stimulating the release of cortisol Paul River was sitting out one night this is the guy back in in 1775 actually a week ago today uh and like 325 years ago or something that 1775 so that math is probably way up but you can figure it out uh he was sitting outside waiting to see these light beacons he was waiting to receive a signal and we could think of Paul R as sort of a uh group of hormones here um and when the signal came in these two light vegans he set off on this path through the bloodstream him on Horseback through the roads uh and with with this message and he didn't actually say The British are coming he said uh boy what was it something like the normals uh something like that I may have written it down uh no I didn't okay well he said some code word and uh basically this this code word if there were proper receptors for it they knew how to respond right so it wasn't just the bridge for coming 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 Riv was going to Lexington the sort of the central Hub this central nervous system brain we can sort of stretch it that way um and and has to find the proper receptors there to to initiate this proper response so uh I don't know I just like that analogy so what we're going to talk about is um hormone back to the neuron has to get through the blood brain barrier um does the neurons it's going to the neuron or the group of neurons do they have the the proper receptors for this hormone signal and uh 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 um starting with the bloodb brain barrier uh so the bloodb brain barrier on the left we have this picture of just blood vessels in the brain um this is here because uh Tom uh sort of has a personal mission uh he and I both have been confused about what the blood brain barrier is what it looks like um he used to Envision you can tell it's just really embarrassing so I'd rather say it myself I used to think that like the brain was in this this barrier that protected it from like the evil blood supply when it obviously 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 confess confessing this to you today today that you actually have to picture the blood vessel's access to the brain in a much more complicated way so the barrier itself is much more complicated as so the barrier is is constructed by basically these epithelial cells lining the the blood vessels right the blood vessels extend throughout the brain is sort of an image of it there and we have these uh this Blood brain barrier created by these tight junctions in epithelial cells um sort of a bunch of details that aren't necessarily super important however it's it's interesting because this barrier this Blood brain barrier basically tightly regates what type of things can go inside and outside the bloodstream in the brain it's it's very important that we have a lot of control over over what's going on um in terms of our blood supply in the brain so hormones the question comes up can hormones pass through the blood brain barrier um we did a bunch of research on this and basically because these are epithelial cells phospholipid bilayer same story steroid hormones um are lipophilic they they can pass through this Blood this phospholipid Bayer um not much of a problem there uh peptide hor hormones um generally we know that they can't pass through just on their own um 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 uh because they have these carrier transports they have the ability to get through the blood brain barrier when they need to um so just sort of an interesting point there first step getting through blood brain barrier it's it's helpful to know it exists it might come up in other context later on things like alcohol alcohol can go right through the blood brain barrier um and that has certain effects on Behavior if we're going to it might come up later on um here's this bloodb brain barrier what can get through it what can't what does that mean what are the implications for that in terms of behavior something just to sort of know about generally so next step uh receptors so hormones when they're traveling back to to the brain there have to be appropriate receptors for these hormones um Tom talks about cortisol an example of a glucocorticoid glucocorticoid steroid hormone this is an image of a rat brain and glucocorticoid receptors in the wrap brain uh we also have mineral corticoid receptors um which we're not really going to focus on in blue an example would be like aldosterone for my MCAT people you know what that is but we'll uh thanks for the nod Nate uh but we're not going to focus on that so glucocorticoid receptors as you can see there are glucocorticoid receptors throughout the WRA brain interestingly however 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 right 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 uh is the hypothalamus um Tom already mentioned one effect of what's going on there potentially sort of these negative feedback mechanisms right glucocorticoids coming back and helping to regulate or downregulate the release maybe I shouldn't say downregulate but basically suppress the release of CR um and and eventually act and other things affecting um cortisols release in the first place we also see these receptors clumped in the hippocampus here um so another interesting potential other type of uh negative feedback thing going on there um stay tuned we may we may hear more about this later on interesting point though is that for every single hormone we're going to have unique receptors um 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 uh we're going to want to be paying attention to when we're looking at behaviors we're we're going to want to look 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 this slide we wrote receptors location type and how many so I briefly just talked about location the location of receptors um how that can matter type of receptors you can have within an individual you can have different types of dopamine receptors for example right 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 populational level right A variation in the type of V suppress receptor and how that can Rel lead to sort of monogamous vers tournament species type behavior um 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 a low amount of receptors not as sensitive um when we look at sort of when we talk about me rats epigenetic mechanisms uh this is 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 um so another thing briefly related to how many receptors we have we have the level of hormone and we have the level of receptors and both of these things basically impact the the behavioral output um an interesting effect we we can begin to see happening is that the level of hormone can affect the U regulation or down regulation of receptor 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 downregulate the cell might sort of downregulate the amount of receptors expressed uh on the on the surface of the cell and and you might see down regulation conversely we might see U regulation if it's not receiving enough of this hormone um stay tuned for more of this comp complexity with this complications with this Etc any questions so far on this stuff okay cool so uh 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 uh we talked about peptide hormones and the secondary messenger Cascades we put the image back up talked about steroid hormones and generally affecting transcription um 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 so we wrote down here we summarized very nicely potential effects of hormones on neurons um once the hormone binds to a receptor we can have it change the membrane potential um via ion channels so maybe secondary messenger Cascade uh if basically some 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 more difficult to start an action potential um something like that uh 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 the DNA affecting transcription of genes um in this case the genes they could be receptors this might be sort of a mechanism for up regulation or down regulation of receptors something like that uh we can also have of course change in protein activity and transport this of course is crucial right um proteins uh could be involved with tons of things uh neurotransmission formation of new synapses the things listed there um basically hormones can have impacts on all of these different areas protein activity uh transcription membrane potential potential all these different things and so at an individual cellular level we can begin to see sort of the wide array of impacts by hormone binding what what that can do if you step back and think about this as sort of networks of neurons not just individual neurons but networks of neurons now you can begin to see how hormones can start to shape behaviors more overall just these networks of neurons these um and those behavioral outputs being sort of the output of these networks Yeah question when you talk about impact on neurons do you mean cells that are in the brain and the central nerv system or just talking about great so question actually can you repeat that for me are we talking whole central nervous system or like just the brain whole central nervous system or just the brain uh so in this case I'm talking about neurons that are in the brain but these might project anywhere as Tom said earlier neurons can project to other areas within the brain can project down the 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 um the neurons right where they project they'll have a certain impact on they'll have some certain output whever they project to uh but in the first place they have to have a receptor for this hormone to bind um so it's just something interesting to note uh other questions that's not a question okay cool good thanks um so I think and that's kind of summarizes my uh thing on that Tom did you have anything to add to that um I'd say the more interesting things that we're when we're talking about neurons changing activity neurons in the brain is where interesting stuff is happening um maybe the lordosis reflex has more of the you know how hormones might influence How likely you are to do your little back arch rays but who knows Okay cool so um yeah so we talked about into the nervous system lectures how Behavior Uh 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 um we're going to give you a little preview of of some areas we might see hormones uh interacting in in future lectures um so uh stress we're definitely going to see glucocorticoids associated with stress response here's uh hairy and serious uh looking sort of stress uh sexual behavior uh testosterone estrogen vas supressant oxytocin we're going to see these things as players in um sexual behavior lectures uh aggression testosterone again glucocorticoids estrogen epinephrine um depression okay I just there's something about that picture all right and depression but oh depression glucocorticoids thyroid hormone estrogen progesterone melatonin um great so some some things yeah just something to add for this slide is we're kind of throwing a bunch of random hormones at you which you might not be familiar with yet um 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 and then I think the last slide is just take home points things that are really um excellent for you to try to walk away with so don't walk away if you don't understand most of these things um 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 depend on whether you're hydrophobic or hydrophilic so it makes it pretty easy to logic through if you know that basic um thing whether you need the chaperone or not and what how where your receptor is going to be um 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 or um endocrine glands and then finally when those hormones are released how can they influence behavior via neurons um kind of the long trials and tribulations of P Paul R really excellent analogy I think I think you guys would all agree um and uh 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 CU you guys have fun things to do today thank you for more please visit us at stanford.edu