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BIOL 3324 Human Physiology - BIOL3324_Lecture04
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00:15 It's always something trying to figure out thing I need to turn up for
00:19 our selling and stuff for s. , sorry about that. I think
00:24 guys can hear me online. Doesn't like a muted today. What we're
00:29 do is we're gonna talk. We're continue where we left off. We're
00:32 talk about signaling. All right, we're gonna look at kind of the
00:38 categories of signaling and just to give cover a perspective. I mean,
00:42 are somewhere in the neighborhood of about or 8000 difference. Different little signaling
00:49 in the body. So, you , knowing how it works generally is
00:53 gonna be like I know everything. gonna cool when you can know
00:58 all right? Yes, sir. earlier. No, it is what
01:12 is. I set it up that for a reason. Oh, you
01:17 be able to see them. They up available at new No, I
01:21 they should come available. Them the . Um, have that student
01:27 Just like email. Dr. Wen that because that could just get setting
01:31 . Um, anyway, eso We're look at the signalling pathways and then
01:35 we're gonna hopefully do. If I fast enough like an auctioneer, we
01:39 get into electrical signalling s. So gonna be really, really fun.
01:44 a quick ride. What you're looking up on the screen, right?
01:47 are some of the basic receptor We have ligand gated ion channels.
01:51 have G protein coupled receptors, catalytic . We have intracellular receptors in cleavage
01:57 activated receptors, which is the weird . It's kind of more of a
02:00 one where you get a molecule and chop it up. And once you
02:04 it up, it becomes activated. doing things. The subset start doing
02:09 on DSO we're going to just kind walk through. This is kind of
02:12 general overview, and you can see what's ligand? Gated ion channel Basically
02:15 channel that bound by some sort of . When you bind that, it
02:19 up and allows an ion to flow . All right. So it's dependent
02:23 a signal to get the channel open allow the movement of free movement violence
02:28 their concentration, Grady. And so is kind of a very quick way
02:32 change membrane potentials, and this will very, very important. We talk
02:35 electrical signalling G protein coupled receptors. talk independently because there are about 5000
02:42 in your body. So if there's 67,000 different type two receptor systems,
02:47 r g protein coupled receptors, so think it's kind of important. Now
02:52 the secret. It's really not 5000 is. But I mean, most
02:57 them are olfactory receptors. And so can imagine I have a sense of
03:02 , like a whole bunch of different . So about 4000 of them are
03:08 So same system, just different. . Well, look at that as
03:14 . They're named four, and you see G protein coupled receptors receptor a
03:19 to a G protein. It's named that. That coupled molecule. That's
03:23 of try Merrick G protein. We catalytic receptors, basically has an enzyme
03:28 one side or the other. So you activated, it activates some sort
03:31 enzymatic activity, and lastly, the receptors. What we're looking at here
03:37 transcription factors that get bound up by sort of Ligon and then once they're
03:44 by that Ligon. They trans locate and initiate or inhibit transcription. So
03:51 changed gene expression. So that's kind the big picture of all these
03:56 And so they're basically six general steps all of these have it is such
04:03 there hit that, All right. so again, what we're looking at
04:07 the picture is a d protein coupled . But I picked. I just
04:11 that their cuts the easy way to it. So the first thing you
04:14 in most cases when you're dealing with , is that you have to activate
04:18 receptor in. So that's when the comes along and recognizes that binding site
04:23 the receptor, and that's gonna activate receptor. Ligand binds receptor causes a
04:28 in the shape of the receptor that a overall change of interaction with some
04:33 of molecule associated with it. So this particular case, you can see
04:37 that G protein there that's Alfa Beta , those three things, that
04:42 that changes the interaction there and activates , that second molecule that what we
04:48 a transducer. And so the transducer sends a signal to some other component
04:55 the South. All right, this will report does transaction. That's why
04:58 name is called a transducer. Some , an external signal and turning it
05:03 an internal signal. I've changed since name transaction, right? And then
05:09 gonna happen is you're going to start mawr and Mawr of what the transaction
05:14 , which is increased the number of internal to the cell. All
05:19 so you get this amplification and what end up with is what is called
05:23 . In other words, this is taking a note in passing that your
05:26 , your friend takes it and copies times and then passes it on to
05:31 people. That's that expansion and growth would be transmission. And then what
05:36 gonna do is gonna change what's going inside modulation and that change that that
05:44 change inside the cell is what we to the response. All right,
05:48 , as an example, I can f s h follicle stimulating hormone onto
05:53 cell like a granule osa cell, is the cell inside your ovaries.
05:57 guys, you don't have ovaries. you didn't know that already. Just
06:02 in case, right. And what is going to do is it's going
06:06 change the behavior of that granule osa . And what that granule osa cell
06:10 doing now is different than what it doing prior to the Fs age.
06:15 not even talking about what the mechanisms the insider, but there's multiple
06:18 and it's this expansive response that the cell is doing in response that single
06:25 . All right now, anything you on, you need to turn
06:30 You guys live with your parents long snow that right? You walk into
06:34 room, you can turn on the , but when you walk out what
06:36 supposed to do, I want to it. I have Children. I
06:41 have to turn off the light. may turn down the temperature, but
06:46 you're are done being in the what do you need to do?
06:49 it back up because who's paying the unbanned bills right. You'll learn this
06:55 you have your own place and you're your own way and everything, even
06:58 you're doing it right now, you're to realize wait. I can't keep
07:01 lights on over. All right, termination becomes the final thing. And
07:06 , what we're trying to do a termination is we're trying to ensure
07:09 the signal or message that we're creating a small, short term response.
07:17 , We don't wanna keep something If we wanna keep something going will
07:21 sending the message over and over So what I want to do
07:28 you don't have this slide because among of your blank slide. All
07:32 But I want you to see the model. Then we're just gonna run
07:35 mall, okay? It's real First off, you have a membrane
07:44 yourself. See, on a great . All right, then. What
07:49 have is we have our receptor. know what your step has the letter
07:55 in it, all receptors have the R. If you looked at it
07:58 a microscope, that should see. right, well, binds to the
08:05 well again. So it has a l Ligon to the receptor. Now
08:09 receptor is associated with a molecule. we call that? We called it
08:13 transducer. And what that transducer is to do is when that receptor give
08:19 bound by the Liggett it's gonna activate transducer. All right, so
08:25 when you say something's activated to give little tiny Asterix or something like that
08:30 what that transducer is gonna do is gonna activate something else downstream. All
08:36 , Now what I'm gonna do is gonna draw it like this, and
08:39 gonna put the letter Z there. usually put a e, but it
08:43 confusing in a moment Z for All right, Now what is the
08:48 do? It does something catalyze is sort of reaction. And the reaction
08:54 you're going to catalyze is going to in usually, but not always,
08:58 usually the production of some sort of messenger. I'll make that a diamond
09:04 point right and what you're going to lots of second messenger. What that
09:09 messenger is going to do is then going to affect the activity of another
09:15 downstream, which is going to affect whole cell. And so what that
09:20 of that second messenger is is called what shape will do now?
09:27 I'll just do a block. We're call that the effect. Er
09:33 so you can see what we have . Ligand binds. Receptor receptor activates
09:38 transducer. The transducer activates some sort enzyme. The enzyme results usually in
09:44 production of a second messenger. And that second messenger's job is to affect
09:51 effect, er, turn on or the effect. Er, all
09:55 And that's for basically every sort of cascade that you've ever seen. Now
09:59 may not always have a second It may be that the transducer activate
10:05 sort of enzyme that activates the Er or you may have the transducer
10:10 the effect. Er, the differences the pathway are depended upon which system
10:15 looking at, but you'll see here a very, very general split.
10:19 mean type of responsiveness. So if understand this, you understand stand 7000
10:28 sorts of signalling processes in the Not about job, huh? Where
10:34 thing you learn them off. Shall prove that this is true? Do
10:39 like something's air rather than bold Would really like to want to see
10:42 evidence? We've got a question. going to find out in just a
10:51 . Question is, what is an of the second messenger? So in
10:55 in one slide in two slides, will see an example of Second
11:00 So here is looking ligand Gated Ion . All right. Now the Ligand
11:06 ion channel is just opening the So you're not gonna have all those
11:10 in place. Really? All you're to do is you're trying to allow
11:12 movement of islands either into or out the cell, and you can see
11:15 the mind What do we have We have a sodium gated channel,
11:20 ? It's bound by ASIO calling its coleene receptor. And so what happens
11:25 when it's E. Coli is released , in this case, a
11:28 It binds that sodium channel, causes channel open and allow sodium to rush
11:34 the cell. The real simple signaling change the concentration of the island inside
11:42 cell. You're changing environment. The Hayes differently. All right, now
11:49 going to see this over and over over again. You're gonna be so
11:52 of this one right here. So not gonna spend a lot of time
11:56 about it. Right? But you gets just here, Open the
12:00 Ion flow in or flow out in case is exploding in. All
12:06 second one is gonna be the approaching receptive right now. The jeep approaching
12:13 receptor. Very poor. Start to discovered. So it's very exciting.
12:19 seven trans membrane. So you can on the outside the cell. It
12:23 the internal region. That's the ligand region C terminal region. Honestly,
12:28 transfer production or transducer Associated region. right. It has seven regions to
12:34 up and down, up and down look like this. That's a two
12:38 model for a three dimensional shape. you kind of get the gist.
12:40 goes up and down several times in six after bottom. All right,
12:44 if I bind something on internal it's gonna cause a change. The
12:48 that's gonna affect the shape of the region. That C terminal region is
12:52 with the protein. The G protein a hetero trimeris approaching, which is
12:57 fancy word for saying three part All right, three parts. You
13:02 a beta gamma stub unit that kind associates itself to those two proteins
13:07 And you have an Alfa sub The Alphas sub unit has GPS
13:11 meaning it is an enzyme. When bound together, it means it's
13:15 It's in active form. All when you disassociate, that means you've
13:21 molecule. And so what happened is Alfa sub unit gets rid of the
13:26 that was normally associated in the inactive and it binds up to GTP.
13:31 now you have energy that you can its All you gotta do is just
13:35 find your enzyme and you can then the enzyme with the energy that you're
13:40 with that GTP. And then once release that energy and you break the
13:45 in the GDP and inorganic bust you're no longer attracted to your
13:50 You're now attracted back to your beta stub unit and so you go back
13:53 re associate. And if you bind to the to the receptor, that
13:59 cause that association again and causing causing to bind up to the GTP and
14:03 repeating the cycle over and over Now I do want to point out
14:08 that we're spending a lot of time we're gonna focus primarily on the Alfa
14:12 unit. That doesn't mean that the Gamma sub unit does nothing. There's
14:17 amount of evidence and pathways that demonstrate the Beta Gamma is also a transducer
14:23 others in other ways. So what have here is a way to turn
14:26 two different things with two different The Alfa or the Beta gamma.
14:30 which ones? You don't need to . What? It's turning on it
14:33 now. Okay, that's the key . We're not interested in learning specific
14:37 . Generically speaking we're looking at is this is a transducer. They had
14:41 question from Hyannis. That's correct. the CEO Colin is like the key
14:54 the door. All right, so you're talking about the Ligon, Eligon
14:59 like a key. It's what activates system. It doesn't come in.
15:02 just simply there to bind associate with receptor and then causing the change in
15:08 shape. So in this case, we're doing, we're taking a channel
15:12 close. You bind to it, opens it up, and I think
15:15 flow through and then it's you calling be removed. All right. In
15:21 case of the G protein coupled receptor comes along, binds to it causes
15:26 changes the shape of the entire which changes its behavior in association with
15:32 transducer. The Liggett never comes in cell. It's always on the
15:40 Now this is Heather G protein coupled works. And I want you to
15:46 if this model looks like what we described in terms of the generic.
15:50 right, so you can see This is RG approaching couple first after
15:56 green thing. There's our Ligon, blue thing purple thing. Excuse
16:01 And then here is our transducer. right, everyone, seal that good
16:08 look what happened. When it binds , there's our activation of the
16:12 The transducer dissociates comes and activates the and then the enzyme results in the
16:20 of and it doesn't show it But it results in the production of
16:23 gonna be in the next slide. production of Second Messenger, which ultimately
16:28 defector And really what this is trying show you here is that we can
16:31 with different sorts of things. What looking at in that little picture right
16:35 there, you can see the Beta is being a game of doing something
16:40 associate with a nen. Zion, out doing? It's associated with an
16:44 . So both of them are acting transducers. And then the downstream response
16:50 is what you're going to see. what the next life shows. All
16:54 , this is the most common type signaling for G protein. You may
16:59 to know this one. All You know this. You understand?
17:03 brooking coupled receptors fairly well. Among a circle thing, just gonna
17:08 through moving from left to right. have your Ligon. It's bound to
17:11 receptor. Receptor is a search of G protein that binding of that Ligon
17:16 the dissociation. You can see the sub unit has activated a molecule.
17:21 enzyme called Admiral cyclists. You might it. Some places at Biddle late
17:27 . It's really try to fund trying say I did a little a little
17:30 little Oh, whoa, Brian. mean, why else would you put
17:36 the end of the world before your gets tired. I you know,
17:45 , I do not know abating ever from themselves. All right. I
17:49 know that it's a three part Typically, how you see it interacting
17:55 as a sub unit together so beta gamma together as opposed to beta by
18:00 . Gamma by self Alfa It's always gamma and Alfa Beta gamma.
18:07 All right, so what you can here is we have our transducer activating
18:12 enzyme admiral Cyclist's job is to take teepee, cleave off two of the
18:21 groups, Take that last fox they Bennett and twisted around. So they
18:25 back and binds on itself. Hits name, it's a MP,
18:31 So it's a mono thaw state instead from try tamano And in that little
18:35 see their front says cyclic and you see in the mult in the picture
18:40 . What they've done is you've taken phosphate. You twisted it back around
18:43 created that bond again. And what have here this site click A and
18:48 is our second messenger. It is of activating molecules downstream. It is
18:54 signal that allows for the implication from single Ligon that you saw on the
19:01 . Does this look like the model I showed you transducer to enzyme for
19:06 messenger? Does that look like Yeah. Okay, now what a
19:13 came PD. Well, it bind from molecule called protein Kind of a
19:19 k a. Right. And this where molecular biology gets really scary because
19:24 too lazy to say everything out So you just abbreviate everything. It
19:28 this alphabet soup of nastiness. But this got to remember is that
19:33 are simple people. All right, there's an A, that means there
19:36 be a B. If there's a , there might even be a
19:40 If there's an Alfa, there's probably bait, and there's probably a
19:44 There's a one. There's definitely gonna a to all right. And so
19:48 can see here we have protein kind a because someone came along. But
19:52 , here's something. It's the parking of be, And there's also perking
19:56 of see, And there's a person of D p. K. A
20:01 just so I don't have to say kind of see how long it takes
20:05 stay parking Kind of say versus PK . Anyway, cycle KNP comes
20:15 you can see your parking kind of has a couple different parts to
20:19 All right. It has a region called a regulatory region, Basically prevented
20:24 doing stepping has a catalytic region when game pekan Long because the dissociation of
20:28 catalytic regions from the regulatory region and catalytic regions can then go on and
20:34 other things it creates, in inside the cell. And so what
20:37 doing now is you're creating a cascade events. The effect, er causes
20:42 effect. Now again, do we what the effect is right now?
20:47 . All right. Different cells do things. And you could imagine it
20:51 just have one target. It could multiple targets downstream. And so what
20:55 now you can imagine is I've got single ligand binding a single receptor that
20:59 the single sex are second messenger. I got lots of second messenger because
21:05 system has kind of been turned and I'm turning these things out faster
21:08 I can count. And now A binding up to this molecule,
21:12 can stay active for a long period time, and it activates a whole
21:15 of different things. And this is my cell starts doing all sorts of
21:20 things because there's so many different things could be turned on downstream from this
21:24 signal another one. That's very, common. All right. Does this
21:35 familiar? Yes, sir. the question is, basically what happens
21:46 catalytic subunits, right? Well, everything. Remember we said with
21:51 everything that gets turned on needs to returned back to its original state.
21:56 what you'll have is you will have helper. There's actually called a protein
22:01 A inhibitor. Basically, what does causes? The Association of Cycling came
22:05 from the PK A, which allows regulatory in the catalytic subunits come back
22:11 , and for every step that you that we're not showing you is something
22:15 turns it back into its original Kind of nice, right? So
22:21 chemical reactions. You look at there's opposite there for every kindness. You're
22:26 boss for lease kindnesses. What? pots for relates puts fuss. But
22:32 put energy in the form of a group onto a molecule. For every
22:36 of those, you have a boss lace that comes along and remove it
22:41 screaming of Boston tastes. I get two bus correlates thinking you think it's
22:48 tastes for I've got it. See here I have in my
22:53 Sure. No, no, no, no, no,
22:57 no, no, no, Is what happens. I get
23:03 especially get excited about this stuff. should know this. This was everything
23:07 did research on. But my brain turned clinic. Sir, I was
23:12 the next slide here. Bust busted stories. Yes, sir. PK
23:25 , PK isn't a factor. yes, yes, I was going
23:28 we're talking a PK. I don't if there's a Yes, PK is
23:32 effect, Er all right, why it in effect, er because it
23:39 and effect. All right? It's the ultimate downstream target. It is
23:45 thing that causes the change. We're look at this again. Here's another
23:50 . This is what your eye So you don't have a real Ligon
23:54 . There is Ligon, but I want to go into a dish.
23:56 We'll wait till we get to the talk about. We'll organise. We're
23:59 activate Colligan. That's actually necessity. approaching couple receptor, you can see
24:03 I've got my Trans use looser in form of a G approach. It
24:07 an enzyme. The enzyme is And then a little cyclists.
24:10 it's possible Die est arrays. That's big, scary work, fossil
24:15 Esther Ace. Oh, what I'm do here is I'm going to break
24:22 di Esther Bond, and what I'm do is I'm gonna take a cyclic
24:26 in this case, likely JMP and cleave that bond turning into GBP.
24:31 now normal instead of that weird, shape. All right, so what
24:36 done here is I've taken something that normally causing an effect, right?
24:43 , in this case cycle, GMP be a second messenger that actually activates
24:47 this particular case, the opening of channel on what I'm doing is I'm
24:51 it from doing so. So can system signaling systems be inhibitor systems?
25:01 , but we tend to think in of the positive, were usually turning
25:04 on, but you can also turn off. Yes, ma'am.
25:18 Well, when the cycle GNP's there , in this particular case because you're
25:21 for this particular model. All All I want you to think about
25:24 now is that I can I have system that works in a very similar
25:29 , right? That's the key thing . Oh, transducers, Turn on
25:32 . Ups. That's when once you out here, walk out of here
25:35 now, worth right. In this case, we're gonna look at in
25:38 eye and after the first test and around three or four lectures in
25:44 I can't remember exactly where it but we're going to see how this
25:48 system is regulated to answer that And it's complex and scary, and
25:53 more you dive into it, but you looking a holy crap. This
25:57 incredible. Alright? Because I like think in terms of binary on off
26:01 actually the way that the system is , it's it's it's not really on
26:07 . It's like kind of tipped right in the center so that you can
26:09 it just a little bit one way you can tip it a lot.
26:13 there's no such thing as 01 It's bunch of smaller things. Okay,
26:21 another one. You're gonna get kind this just trying a hammer point
26:26 Here, see the receptor. See Liggins to the transducer. Ligand binds
26:33 transfusion gets turned on it Done in on enzymes Foster life a c with
26:39 beta. So if there's a there must be a Al right
26:44 actually, several of them. And troop, also for the Boston illustrates
26:47 . Now, this is what bus like. Pasty. Does Boston Life
26:51 . You can see my face. going to cleave a fossil lipid one
26:56 possible lipid is gonna clean? Maybe we like named earlier in the previous
27:01 ? Yes, fast one Ostfeld iPod Bokkelen ASAP. Oh, all
27:04 And what you have here, you see there's are possible non settle.
27:07 actually pip to, is how we it. And what we're gonna do
27:10 we're gonna clean that. And what get is a long fatty acid.
27:13 still triphosphate. All right. And are left over what they die.
27:19 silk cholesterol that's sitting up there and remembering, All right. And so
27:23 we end up with is we cleave . And so what we now have
27:26 have a second messenger. All here's our second messenger. What's your
27:30 messenger doing? It's causing something else turn on. This case is acting
27:35 a Liggan to open up a channel the cell. Right. Okay,
27:41 we got another mechanism. Enzyme results the production of second Messenger.
27:45 we all have another second messenger diocese . I die. Cyclosarin activates a
27:50 kind ace happen to be protein kind see. And what do you
27:53 Is a result will now have an . Er that's getting turned on.
27:58 what protein kind of see that So what? We have ligand
28:04 Receptor turns on transducer. Transducer turns enzyme. Enzyme activates second messenger.
28:10 also results in the activation downstream of E for effect. Er, do
28:18 need to go back to the original to show you the whole pathway?
28:22 . You're starting to get it right . This is what possible life pasty
28:27 does Basically activates a molecule called Cal in right. That calcium that comes
28:33 of that cell or out of that Sorry. Let me back it
28:37 But I just got all excited. here. Open up that channel.
28:44 comes out. Alright, Great. , what is calcium? Two counts
28:47 as a messenger to second messieurs, activator sort of the binds to a
28:52 called Cal Module in. Okay, , This is just so that you
28:58 wrapping your mind about Randall language. Modular. What does it do?
29:01 is modulated. So modulated protein, , modulated protein. Forget it Got
29:07 name from And what it does is activates other proteins. So it's also
29:13 effect. Er that is affecting you see. So what is an
29:19 ? Er do it causes change? we care what the changes right
29:25 One last system just to prove a bracket on a gas. Oh,
29:30 goodness. Record. Donna casted. our system. You look up there
29:34 we start with ligand binding receptor. you transducer activates peel a to plus
29:39 light pace a two. There's two must b'more, right? And then
29:45 you do is you get all sorts calcium coming out of the cells telling
29:48 why. But one of the things the process of doing whatever possible I
29:52 a does basically cleave the fossil and it results in the production of
29:58 racket. Danek acid when you hear word it racket, Danek, what
30:01 you think of spiders? I don't why. I mean why they call
30:07 record, Danek. But when I it, I think of spiders.
30:10 it's just because long and stringy. don't know. I could probably go
30:14 it up. All right, But can see here right here is my
30:18 lipid. I cleave it. I this long fatty acids change to record
30:22 acid when Iraq a tonic acid used tons of stuff. All right,
30:29 seeing I'm making From that activation, creating a molecule that could be turned
30:36 ah, whole bunch of different types signaling molecules. In other words,
30:40 types of defectors. All right. you've heard of many of these
30:45 right? Have you heard of a ? Yes. No, Maybe.
30:51 right. Process Clinton. They're responsible contractions throughout your body. All
30:57 primarily, you think about them in of labor. All right,
31:01 They're called prostaglandins. What do you they're named after? Based on the
31:08 prostate gland? Because they thought it from it. Actually. Turns out
31:13 not from the seminal vesicles in the , but if they thought the prostate
31:16 question from the audience. So the meeting on the bingo, because today
31:29 not talking about any specific pattern, ? We are only learning the generality
31:35 understanding this and this is really the thing. This is what differentiates learning
31:41 you're young versus learning. When you in college, in when you're
31:44 you memorize here. We're going to ideas in concepts. If you learn
31:50 concept once you've learned all of remember their 7000 of them but wants
31:56 memorize 7000 different pathways of the 1234 seven people here. Zero hands were
32:03 right, although that home have any you guys raise your hands? No
32:07 , no one has raised their No one wants to memorize 7000
32:11 Let's learn one thing and then see supplied over and over again. All
32:16 , that's what this is trying to you. Oh, it's also responsible
32:19 regulating information. Ever had a Right. Guess what's helping you,
32:27 that how do we stop a We take aspirin. Well, nowadays
32:31 take ibuprofen. Other anti inflammatories, ? But right up there at the
32:35 . Let's see. Where is Cox. You see? Right
32:38 Talk a cycle. Oxygenation is right there next year. Economic asset to
32:42 left. Hard to read it, . That's what aspirin blocks irreversibly.
32:49 have to completely replace all your cocks order for you to start doing
32:55 All right, so I just showed basically g protein coupled receptor. But
32:59 true for all of these. So air the catalytic receptors, all
33:03 And again, you don't need to the specific receptor types. It's just
33:06 we come across them. Oh, . I can see how this is
33:10 now. All right. So you see a receptor region. You have
33:13 enzyme region that typically found on interest fluid side. So typically, these
33:18 as die MERS, so you have actually have to molecule buying each of
33:22 one for each and then they come . And once they come together,
33:24 when they become active. And then you're doing is you're activating the design
33:29 the end, and then you basically the same sort of stuff,
33:33 The differences is you don't have a . Usually usually what you have is
33:37 enzyme is doing all the work of things downstream. So, you
33:42 do I classify the second messenger? , I classify. This is in
33:45 , er it doesn't really matter at point, but I want you to
33:49 it's the same principle. Ligand Receptor receptor activates an enzyme the enzyme
34:01 the production of usually second messenger activates molecules downstream to cause and effect.
34:09 ? You guys heard a rash so some people have. All
34:15 you haven't taken cell biology and molecular yet. Some of this stuff is
34:19 . You guys heard of this right ? Map kindness, maybe. Sort
34:26 . Yes, man. Not It's just as an example. So
34:34 that's just that these air many of air example. So right up
34:36 you see that map kindness, Map Oregon their molecules that sauce for late
34:41 molecules and then the downstream, effective map. Kindness might be mapped,
34:47 A's kindness. And then there's Matt kinds kind. Is Matt kind of
34:52 of kind of kind of map kind kind of kind of kind of kind
34:55 map kind is kind? These kinds find his kindness. And I think
34:59 one more map kind of kind of of Chinese Chinese. Chinese kindness.
35:08 , they're not really. Biologists are original people. Very, very
35:12 Very stupid names. What? This just credit should look. It couldn't
35:18 for lead side of solid proteins. can cost for, like, transcription
35:21 that basically turns on or turns off moment. That's really what this is
35:25 . All right, so some single , not all typically speaking when we're
35:33 with single transaction, that's everything that just kind of looked at results in
35:37 activation inactivation of psychedelic proteins. In words, what's already there gets turned
35:42 or off. All right, right. What's gonna happen is,
36:00 you're gonna have something that, ultimately for, relates a transcription factor,
36:05 then once that happens, then you're to get transcription or in activation of
36:11 . Now it's always have to put place because again, we like to
36:14 in terms of when I turn things , you know? Or whenever I
36:18 system, I must be activating There's cases where you're actually turning off
36:23 at the same time, all And so again, it's not so
36:27 that, you know, yeah, is going to cost for late,
36:30 know, transcription factor, and do or jak stat is going to be
36:34 to the possible relation of transcription We look at a specific system and
36:39 using. That's when you learn I just want you to see that
36:43 are ways to activate transcription or inactivate by the presence of of these kind
36:53 pathways. Normally, though, when want to activate transcription or inactivated,
37:05 what you're gonna do is you're gonna a lipid soluble ligand. All
37:11 In other words, what you're gonna is you're gonna have some sort of
37:15 cool that's capable of passing through that membrane. It doesn't need a signaling
37:20 . It's gonna passed through the plasma bind to some sort of molecule
37:26 In this particular case, we're looking a heat shock protein again, not
37:29 important. But what happens is is is that he chucked cooking. That
37:34 room brings it to the receptor that's a nuclear receptor, so lipid soluble
37:41 bind to nuclear receptors. Nuclear receptors called nuclear receptors because they trans locate
37:48 the nucleus. That doesn't mean that always live in the nucleus that can
37:51 in the side is all or in nucleus. But once they're bound to
37:55 leg in what they do, is trans locate to the nucleus.
37:59 they form a dime er, and once they form a dime,
38:02 that's when they're capable of binding to . And they want you by the
38:08 , your now serving as a transcription . All right, so it's a
38:14 , very different sort of system We don't have a cascade of
38:18 It basically I bind trans locate. initiate a response. No, the
38:29 in this particular case is the production a new protein. Yes,
38:39 no, in fact, their That's what I'm trying to get
38:42 All right, These air slower in of the response. Now,
38:48 all right? The reason why it's same reason why this room, if
38:53 flip a switch the light turns on can think of all the things I
38:57 to make this room Bright is already the walls and hooked up to a
39:01 switch. Right. So I got do is act as the Ligon to
39:05 receptor, which would be the light , and that would make the lights
39:08 on in the room. Would you ? Really quick. The nuclear receptor
39:14 is saying, Oh, I will you all the materials to put all
39:18 things up so that you could light a room, but you've gotta build
39:22 . Okay, so I'm gonna deliver the wires. I'm gonna deliver you
39:25 the outlets. I give you the , I'm gonna give you the
39:29 but you've got to put it which you think would be faster to
39:33 on the lights number when it's already up or one that you have to
39:39 . What do you think? You the answer. The former. I
39:47 the plug stuff. So with this , what you're doing is you're turning
39:51 the genes that makes all the proteins are now causing the change in the
39:58 that you're looking at all right Transcription of the fast process. So
40:03 very quick and that, but again effect that gene has to be transcribed
40:11 ? You got to translate the gene a product product. This is able
40:18 . It's there is a significant lag , but the differences and I I
40:23 to get here is that with the cascade, while the system is very
40:28 , it also turns off quick, , so I can go and turn
40:32 on. And then as soon as turns on Railway said, it's gonna
40:35 it right back off again. Turn . Everything you turn on, turn
40:39 . With a system like this, gonna take a long time to degrade
40:44 molecules that you have created are they half lives right? The proteins that
40:50 make have half lives, and so things are being made and they're going
40:54 stick around for a while. So have an extended period of time in
40:58 those molecules will work. So they a longer life spans in terms of
41:02 effective. Because diamond ization is when things come together think what is a
41:10 ? But generally speaking, dime are things. So it would be two
41:15 the same coming together. And that's this is trying to show you.
41:18 got the hetero dime, er, right, so I'm going to show
41:22 the hetero dime. Er, I'm gonna circle it in the picture.
41:26 timer would be that two different but slightly the same home a timer
41:32 be through the same. There's your , a timer, And depending upon
41:39 sister we're looking at, there might hetero timers or home on timers.
41:42 worry about it right now. You me about interference. I don't remember
41:54 about interference off the top of my . In terms of of Well,
42:01 , I can. All right, can. All right. So if
42:04 give you interferon gamma to deal with infection, right. The response in
42:10 cell is gonna be very, very right here. Parents gonna buy an
42:13 . You're gonna get signaling. Cascade going right. I give you a
42:20 , right? Cortisol foreign. What's have to happen? Steroid has to
42:25 an interceptor. It's gonna turn on bunch of jeans. Gonna take a
42:28 to get a response. All So I'm gonna make up numbers,
42:33 don't be. They're not numbers you to the bank. You can get
42:36 response in a signaling cascade. In matter of seconds, you get a
42:41 in a nuclear receptor cascade or nuclear response in a matter of minutes.
42:47 right, seconds versus minutes. Just give you an example, I used
42:51 working lab. I dealt primarily with hormones to, you know, rat
42:56 . So I give him FSH. acts through a signaling cascade. I
43:01 get a response in a matter of seconds. Literally. I could put
43:05 chemical on, and I'd have to the reaction on. Isil is immediately
43:10 try to stop it Exeter and you the temperature real quick. So the
43:13 and go forward, right A matter seconds. When I give something like
43:18 or estrogen, I could the first a van a look at it somewhere
43:23 15 minutes There. That's the idea that there's different. There's a significant
43:33 right, Maggot e, Why But all right, whatever.
43:44 hopefully we're still recording with teens. , that's why I always did
43:53 Because I know if you noticed there a couple of them where it wasn't
43:56 same recording that she Well, all . So let's let's kind of move
44:00 here. So when looking at these , what I want you to do
44:05 I want to do these nice simple for yourself or little charts. There's
44:08 easy way to do these Compare You can see what is the membrane
44:12 step to do? What is the step to do these air characteristics?
44:14 should compare it. If you feel like this out, it'll be really
44:17 for you to kind of go. , yeah. I can see the
44:20 between these two. We're gonna do in class. That's something into
44:28 Now what? This does lead us another question. Because really, what
44:35 talking about here is we're talking about talking to each other, right?
44:39 all these mechanisms could be done using or peregrine or long distance signaling.
44:45 I want to talk and shift more long distance signalling. All right,
44:49 does this body talk to itself over long distances? In one of the
44:53 is through these long distance molecules that call hormones. All right, So
44:58 are typically secreted, um, in are called glands, and these are
45:02 examples of different lands, right? a tissue that's derived from an epithelium
45:08 , not so important to you because it's not an anatomy class.
45:10 not learning these different things. We secrete by an individual cell something shown
45:15 this picture. Weaken, screened by neuron weaken secrete by individual cells that
45:21 like in the immune system. We these things different names and in
45:26 that line between what is a hormone what is they? Just a long
45:29 signaling molecule has kind of blurred over , the longest time, ah,
45:34 with a hormone. And that was end. And then we started discovering
45:37 that are signaling molecules is like, , well, maybe there's more to
45:40 than what we understand right now. hormones excreted in the bloodstream, but
45:47 do have some hormones, like ecto is a fancy word for things like
45:52 . We do secrete things out into external environment. All right, that's
45:57 signalling molecules. We just don't do lot of that. The targets are
46:02 be. Like I said, it be a local thing or it could
46:05 some distance away. The key thing that the target cell must have the
46:10 of for that particular signaling molecule. order for it to respond, we
46:18 all sorts of hormones into our They're in constant circulation throughout our entire
46:23 . But not every cell in our respond because they don't all have the
46:27 receptor. It's just the cells that right receptor, they're responsive.
46:31 when you're dealing with hormones, you're with incredibly low concentrations of these
46:38 right? So we're talking in the of PICO Moeller concentrations, so literally
46:45 little tiny molecule can do a huge response. All right, so
46:51 is very, very low in the . Trying to measure it is
46:53 very, very low now. Harm classified my lunch different ways. All
46:59 ? We can do it in any that you want, Teoh. I'm
47:02 try to point to what I think the easiest way. But one thing
47:06 they do is where did that come ? What is this? What's its
47:09 ? Is it a neuro hormone is glandular hormone yada, yada,
47:12 They didn't make a lot of sense me, so we just kind of
47:14 that, All right, How does hormone at another word? What type
47:20 receptive you? That's a good But it can get kind of confusing
47:24 of some of the complications in terms the classes. And I actually even
47:28 an email about this earlier during office . So you're building water, I
47:33 , is a valuable one. That's really, really easy way to do
47:36 , because it allows you to think terms of how it acts on those
47:41 . But again, there's that And so probably the easiest way to
47:45 hormones is along. The lines of are so the chemical class. We
47:50 peptide, or protein hormones right G H R E growth hormone releasing
47:55 . That's a small peptide that looks a pep type. You see
48:00 you see the in terminal region See the C terminal region? Not
48:06 well. It's been kind of all right. We have things that
48:10 steroids. There's cortisol, all that's steroid. And then we have
48:17 . That's Inamine. It's been Amino acid. Start with the original
48:22 acid do changes to it. All , three classes. But what?
48:26 going to take those three classes and look at those middle to How does
48:30 act and what's its eligibility and And so what you can do is
48:35 can kind of think in these few if I understand peptide and understand
48:39 that I understand the middle to soy and water mechanism of action. And
48:43 I got that weird class, the class, which kind of falls into
48:47 other two in terms of behavior. want to start with the pep
48:51 all right. They're really, really , we're going to look at how
48:54 made, how they're stored, and ultimately, how they're released. How
48:58 they transported in the blood? And , how did they act? And
49:02 peptides or proteins are made like every protein, all right, their start
49:06 his large precursors starting the interplay of particular moves, the Golgi modified
49:12 And then what you do is you chopping it up in the little bits
49:16 their into their active forms, and storm away until it's time for
49:20 So you keep him in these and so what you need is you
49:23 some sort of signal to cause release you're making these not so much in
49:29 constituent of way, but and as to a constituent WWE as you possibly
49:33 . All right, So what you're with is I have it. I'm
49:37 waiting for something to tell the cell release it. And then once you
49:41 it because it is a peptide, gonna go out of the blood.
49:44 it is half in the blood. is primarily water. This is a
49:49 soluble molecules. And so, being soluble, that means it can pass
49:55 the blood, sit around, be happy without much problem. Now,
49:59 I say that, that's not apparently , okay? Because anything you put
50:03 the blood is once. If body want it around, it's gonna chew
50:07 up. And so they're enzyme they're to destroy. And so there are
50:10 for some of these things. But the most part, that's just to
50:13 the half life. So water soluble like peptides and proteins are constitutive.
50:23 made their stored up there, released some sort of signal. They go
50:28 the blood, and they are freely through the blood, usually not without
50:34 carry, but they can have And then what they do is when
50:40 get to their target, the receptor going to be found on the surface
50:43 the cell. And so it's acting a membrane bound receptor. And ultimately
50:51 is signaling cascade. Simple right water actress ing our second not second guessing
51:01 through a membrane bound receptors. Now this is trying to show you is
51:06 source of hormones. You don't have memorize anything. But you guys all
51:10 of insulin, right? Yeah, it starts as a large precursor.
51:16 gets cleaved. So there's the insulin in terms of a two dimensional
51:20 And then there's the byproduct. All , you can see up top.
51:24 Ah, uh, read it any appropriate Trh you can see that's a
51:30 large precursor. It gets cleaned, end up with a whole bunch of
51:34 and a whole bunch of other junk you don't need. Here in the
51:38 , that's propio male. In the , it's cleave that you end up
51:42 three different types of hormone, And this other junk. So we're
51:48 off with the big calculated Do something you chop it up and you get
51:51 whole bunch of active signalling molecules. what this is trying to show
51:57 So again, what's the mechanism of action? We don't need your creature
52:02 little step, but you can see these molecules look familiar to you?
52:07 , we got G protein coupled receptor protein coupled receptor G protein coupled
52:11 Look over here. What we We have a bunch of enzyme
52:17 so they use membrane bound receptors. the peptides roids Oh, this is
52:30 fun when I love showing this for freshman class because they think they have
52:33 memorize it like this. This is usual basically the major class of
52:41 Steroids all start as cholesterol and then the pitting on which, in
52:45 the president in the cell type of the hormones being made. You're going
52:49 get specific types of steroids. So just want to kind of show you
52:53 , that you can see this yellow other than the progestin. Those were
53:00 androgens. Those were the estrogen's, peer of the melon cordons. And
53:05 here, that is the, glucocorticoids excusing us in there. And
53:12 don't see the adrenal dream stuff, those arguing, all right, you
53:19 don't hurt of progestin. It's where the protest is normal. Produced
53:27 a period of time in a woman's . Do you have, if you
53:30 to guess, huh? During pregnancy says the name pro gestational form of
53:39 progesterone. All right, Now I to show you how important it is
53:45 the people who report on science should a little bit about science because they're
53:50 in this world, all right? they have a major impact on your
53:55 . So I don't know if you heard this was, uh I think
53:58 was in the fall of last but it was some social justice.
54:03 who didn't like men, and this in Britain, and she she had
54:07 influence that her stuff was being published the new stuff. And she was
54:12 , Mitt, experience what is like women to go through pregnancy? All
54:17 , I'm not gonna pretend like Easy. I thank God every day
54:21 I'm not a woman cuts, you , guys going? Yeah,
54:27 we get it up there so, know, pays off one way or
54:30 other guys are laughing. It's just , guys, it's not misogynist
54:37 So this woman says Whitman need to and see what it's life. So
54:41 we're gonna do, I want a . Men with progesterone. All
54:46 Now put apart all that all sorts inhumane or the human rights violations that
54:52 be, but, you know, how hormones made right and what I
54:58 said, it depends on the enzymes you have present in order to make
55:03 . Now, look at the cascade here. This is the fun part
55:07 Point is up there in the top at is cholesterol. What's the first
55:12 of steroids that are produced for both and women? What's the yellow
55:19 What did I tell you? It's there. Yeah, him,
55:24 Oh, it for a soon. right. And then have the enzymes
55:30 make which types of hormones when you a male hormone, What do you
55:36 ? Testosterone, Which are the androgens where the androgens located right there.
55:50 if you get guy as a whole of progesterone, what are they going
55:52 do with that progesterone? Are they feel like pregnant ladies? No.
55:58 gonna make crap ton of testosterone because do not have the hormones or the
56:10 that pushes over here and make a of the estrogens. Now, few
56:13 make estrogen's. We do, but primarily make tend in times of
56:20 So this very, very bright woman probably never had taken a single biology
56:27 you never bothered to understand process. knew big words didn't understand what would
56:33 the consequence of her plan. In , I think it would be the
56:38 opposite. So how does there? work. Their lipids can store a
56:47 inside of ethical. What do you ? No. Now I can't store
56:57 and lipid, but I mean, can put him in a lipid
57:00 but I can't could put on a school. So I make steroid As
57:05 as I get the signal to make , all right, and I make
57:09 and it immediately goes out into the . So there is no storage.
57:14 basically made as a result of some of signal said, make steroid.
57:18 body's okay and you make it It goes right on the blood
57:22 And remember, it's a lipid. want to be in that watery environment
57:25 the blood. It says, note. This is not where I
57:28 to be. So the first thing does it binds up to some sort
57:32 molecule that can hide in sequestered away the water. Lipids are excluded from
57:37 , so you need something to help hang out in the water. So
57:41 needs a transport molecule. Now, , we have a whole bunch of
57:45 types of specific carriers. Example, have appeared I'm just trying to show
57:49 is a corticosteroid binding protein. All , so this would be for a
57:53 of all, for example, you court is all, there's a binding
57:56 , so I recognize you and it up and gives a giggle.
57:59 I'll carry you in the blood for long as I need, but we
58:03 to have non specific carriers. You heard of albumin? Yes.
58:08 No. So go home night and an egg open and look at that
58:13 , clear stuff that's predominantly albumin. a little itsy bitsy. Teeny tiny
58:20 that's found circulating in your blood actually a lot of your blood. All
58:24 are just instant. Lot of in doesn't make up the blood sensitive lot
58:27 circulation. It's a non specific, protein. It's a carrier molecule,
58:32 you combined up to it. And this protects that ends our that hormone
58:38 being destroyed now, obviously gotten bound . I can't pass through a plaid
58:43 , and the very purpose of its is to pass through. Apply the
58:46 because my receptors are nuclear receptors, there's actually a ratio, a dynamic
58:55 . What I would say between wrong that's were looking for between the amount
59:03 hormones free floating and the amount of that is bound up to that to
59:10 carriers. What is that ratio? matter. Just imagine 1 to 1
59:15 by four molecules of hormone in the , then two would be bound to
59:20 unbound. All right, if I to, one would be banned when
59:26 be unbound in a perfect ratio What if I only have one
59:34 What did you guys learn in I need to bind something up and
59:38 only have one. And I have perfect ratio. What you gonna
59:42 Think about a chemical reaction. You those double arrows, don't you?
59:47 It goes. This one goes that it goes this way to goes that
59:50 , Well, that's what that molecule . It's been part of its time
59:53 part of time off, and this how we can get it freely disassociated
59:59 was freely available. And so in places where it's like I'm free,
60:03 might actually work its way into a and their carriers and other stuff in
60:07 kind of hold on seaQuest from there help associate them with the proper nuclear
60:12 . When one of the lipid bad or these lip of Filic molecule binds
60:17 a receptor. Remember, What does do? It goes into the cell
60:22 sorry into the nucleus not to Starting in the cell into the nucleus
60:27 with another lipid down, Ah, nuclear receptor activates or not, actually
60:35 the DNA and regulates transcription. All , so this It's kind of what
60:44 looks like here you can see in little picture. We have a freely
60:49 disassociated steroid. It's not bound to carrier at this point. Spending habits
60:54 on half its time off goes into cell. It's picked up and associated
61:00 the nuclear receptor nuclear receptor. Trans , finds a dime er or creates
61:06 dime. Er binds to the DNA the shapes transcription over a little bit
61:12 time, you get the protein. say that one more time.
61:26 Oh, so they're not completely remember spending a portion of their life span
61:32 , Assoc disassociated and part of their span. Associating each hormone is different
61:41 terms of how long it's gonna Associate it or not. So we
61:44 we don't We don't make any but we need to recognize that they
61:49 both states. There's abound. Statement state. It's when it's in the
61:53 state that it's really available to go a cell within the bounds state.
61:57 can't in the bound state. It's gonna be destroyed by enzymes. But
62:03 the end, downstate, it could crime. That's the idea.
62:08 I answer back what else it's That study means the means are the
62:18 ones they sit in between. These hormones that are derived from either trip
62:25 fan or from piracy. All so you're familiar with the amino
62:30 Oh, the too big one. then what happened is upon which type
62:33 hormone you're making. The trip to makes melatonin. We're ignoring that
62:37 because right now we don't care. seen the family cat a cola means
62:42 thyroid hormone catacomb means behave like They bind to cell surface receptors,
62:50 they initiate a cascade all right, scene. Behave like a steroid.
62:56 binds the nuclear receptor, initiates its through its particular nuclear receptor. So
63:03 is why this particular group is a in the butt because while class
63:09 we can see how they're made from and you can see there's original tire
63:13 . There's modifications, right? They're of them. Behave one way,
63:17 of a behaved the other way. so it's just a matter of
63:20 Recognize? This is the one that's . I've got to remember which one
63:24 , which. This line right here showed you how the catacomb means
63:34 And so again, it's just showing we have a risk. Us membrane
63:38 receptor acting through signaling cascade. Now , what's the easy thing to do
63:44 ? Make yourself a chart. Print one up and just fill it
63:48 How's it made? Has this? Has a store, which it's looking
63:52 scalability? Has it moved? Where the receptor located? Is it cell
63:57 bound? Remembering banner sector is a receptor. What's this mechanism of
64:02 What's the rate of response? Slow All right and fast or sit
64:07 bound slow for, uh, And it's all relative. It's all
64:13 relative to us, right? But staffer than the other. Now,
64:21 to make life really, really difficult us, hormones have these really,
64:24 funky rules. First funky rule is you can have a single into Kringle
64:29 make more than one hormone. so great example of the anterior.
64:35 has six different hormones that it In fact, we consider the master
64:38 because it produces so many different All right, you can have a
64:43 hormone produced by different tissues, so have a molecule called somatic staten.
64:48 made in the pay increase. It's made in half elements, depending on
64:51 it's made, it has kind of role. Alright, single hormone can
64:55 more than one type of target, all right, so I'm using insulin
64:59 the example in the insulin typically acts muscles, right and liver and fat
65:04 other tissues to cause the intake of . All right, on muscle that
65:09 doesn't take up glucose. Instead, said, you've got to do other
65:13 . All right, the rate of of the hormone can very over a
65:19 , the easy one to think about menstrual cycle you can think about the
65:22 of estrogen starts off very low and higher, higher, higher, and
65:25 it gets alot again, and it of does this kind of really strange
65:28 form. Same thing with LH and . That's the easy one to
65:34 because we're probably most familiar with But there's also other ones you've heard
65:37 circadian rhythms. Those help modify and how hormones are produced cortisol being particularly
65:44 and that it has a daytime production that changes. Furthermore, other weird
65:53 . Uh, some cells, the cells can be influenced by more than
65:58 hormone and in some cases, one acting as a gas. Someone's acting
66:02 a brake. All right, that were trying to show you insulin.
66:06 , a gun are basically opposites. and progesterone can act as an opposite
66:12 terms of uterine contractions. Estrogen promotes . Progesterone prevents contractions. Obviously,
66:18 you're pregnant, you don't want contraction way to the end of pregnancy,
66:24 . All right, um, this the begin, that blurring of the
66:28 , what is a signalling molecule versus is a, you know, like
66:32 neuro transmitter, which will learn about little bit later. They can be
66:36 or the other, depending upon what you're looking at. So if you're
66:40 at something like, say, norepinephrine It's for secreted by the adrenal.
66:44 is part of the endocrine system. goes in the bloodstream uncertain, circulates
66:48 the body and act like a But it could also be released by
66:54 fibers by the nervous system, in case is acting like a neurotransmitter opening
66:58 channels very confusing all right, and matters worse, we can look
67:04 and we're going to say, You what that is an endocrine organ.
67:07 some endocrine organs are slowly endocrine in . In other words, your glands
67:11 all they do is to create other , have multiple roles. Easy ones
67:15 the reproductive organs. Attach is in ovary, for example, are responsible
67:19 producing AM eats as well as producing . And then we really want to
67:25 the lines. Just think of every in your body signals to other
67:29 You're the digestive tract. Your for example, produces hormones to regulate
67:35 your cells are responding to the food you're actually processing. Would you ever
67:41 of the stomach is an endocrine No, you just think of it
67:46 the thing that grinds up food. right. Plays a role in
67:50 So Theo endocrine system and hormones are , very complex when you look at
67:57 broader picture. Lastly, hormones have of some unique activities when it comes
68:05 other hormones, their permissive what that is one hormone allows another hormone to
68:10 its thing. And so the example is for thyroid hormone, all
68:16 and this is in from the reproductive . We know if we give a
68:20 FSH and testosterone, it's test usual , but it will never be able
68:24 produce firm. Isn't those the two things you need? Yes, but
68:31 need thyroid hormone to make it possible sperm at a genesis to actually take
68:36 before the other two things work. of one of these weird things.
68:40 just an example there. Synergistic, means that they're complementary. And this
68:44 what I call biology math, not biology, which is far more
68:48 This is just ageism is biology, . See everywhere in the world,
68:53 plus one equals to write, but biology, if you take one and
68:57 it one next that you now have right? Thank you. It's funny
69:04 you were in class should be able see the joke. Right? But
69:09 how it works. See? And is what the graph shows you.
69:11 epinephrine. Glucose looking gonna quarter though of them are pretty weak in terms
69:15 their responsiveness for producing blood glucose Alright. Increasing blood glucose levels.
69:20 . So there's your one year one one. Put Google on epinephrine
69:24 You know, it goes up all doubles it doesn't it. All
69:28 you know, and then put all of them together and you're through the
69:33 . One plus one equals 11. . I know it's visuals. This
69:41 hard to teach without people in And antagonism is basically when two hormones
69:46 fight each other and what they're really is there dan on regulating the presence
69:50 their its receptor? So the example have here is projector in estrogen in
69:54 of uterine contractions. I told you promotes contraction. Progesterone inhibits contraction.
70:00 the only way those two hormones can is if they're receptors present. When
70:04 levels are high, they down regulate receptors. Right? When progesterone,
70:12 , progestin is present, it done regulates estrogen receptors. And so,
70:17 pregnancy you have a little bit more than you have estrogen. So you're
70:20 down regulating the effectiveness of estrogen because removed the receptors from the game.
70:28 even though the hormones there has nothing can respond to it right, that
70:33 be antagonism. And I'm going slow semester. Part of it is because
70:42 heavy pause and stop. I I normally pause when I'm talking,
70:46 yes, there's a lag time. what I want to do is I
70:50 want to kind of look at just one of the major endocrine
70:55 This is the pituitary gland. It's a little tiny thing that looks
71:00 an upside down mushroom underneath the Basically, if you want to put
71:05 hole through the top your mouth, could get to the pituitary gland.
71:09 two parts to it. We have anterior in the post. Your pituitary
71:12 here is facing this way on your . All right, this would be
71:17 theory on that side. Okay, , anterior, with little aero post
71:22 is a fat arrow right now, two halves to this particular gland have
71:29 origins in terms off developmental origins. anterior huts half is landler Nature.
71:36 post here portion is neural in All right now, really, they're
71:42 neural in nature, but one is neuro epithelium. One is not
71:46 One is actually nervous tissue, and that's the difference. And so what
71:50 is this structure is regulated by another in the brain, called the
71:54 Patel omits the hypothalamus, produces hormones regulates the hormones of the end
71:59 or sorry of the pituitary, how regulates there. And so that's what's
72:04 there. At the top is the . There's your elements of here.
72:09 so for the hyped elements Puck, anterior portion it does throats does so
72:14 a vascular link. In other through the blood, it releases hormones
72:18 into the blood. Blood is, , small shunt, a portal system
72:22 go directly to the anterior pituitary, it talks to to the cells inside
72:27 anterior pituitary tells it what to do terms of releasing hormones. The post
72:32 is side, On the other is a neural link. In other
72:34 , easier neuron that originate up here the hype elements, and then their
72:40 traveled down into the post here And that's where they terminate. And
72:45 when you stimulate the hypothalamus, it the release of hormones from the post
72:49 pituitary. So we call it a pack away. It's not the hypothalamus
72:54 to the post eerie er, it's the hypothalamus is continue down into the
72:59 here. All right, so what have here are two different structures that
73:06 hormones and different ways. And so I want you to think about here
73:10 I want to look at the post first. It's really, really
73:13 all right. There's two hormones that being produced. It's a th right
73:18 vasopressin. A. T H is diuretic hormones. Have you heard that
73:23 ? Same thing. And the second is oxytocin. They're very, very
73:26 related. I think the difference is single amino acid. Other species only
73:32 one of these molecules. So for example, only have oxytocin so
73:39 , present or a th. well, we'll get to that in
73:42 seconds. So, as I the cell bodies are up there in
73:46 hypothalamus that's where you're making the You transport it down into the,
73:52 uh, to the terminal region of neuron. And it's from there.
73:56 where you're gonna release that those of hormones right now where these cells originate
74:04 in two different regions. It's I mean, so you have the
74:09 optic or the pair of ventricular All right, now, again,
74:12 is not a nanny class. I you guys get yourself prepared when you
74:15 the word Super optic break that word from a super What does it mean
74:22 ? Okay, optic. Hi. . So So already, states of
74:29 optic nucleus means above the optic right? So it's gonna be the
74:35 nerve. All right, so it's it's just a direction, all
74:39 There's no impact. A ventricular soap next to, and the other half
74:45 a ventricular or right, and so refers to the ventricles of the
74:50 So next to the ventricle nucleus, just a direction. Just tells you
74:55 located right. When you get into anatomy environment and you start seeing these
75:00 that are literally like this, just it down Okay. The connecting point
75:06 and point B. So these two eyes were these. These neuron
75:11 A single neuron will only produce one of hormonal leader produced that suppression or
75:17 oxytocin. But each neuron could originate or the other. So it doesn't
75:21 that all off steps and comes from super optic or the pair of ventricular
75:25 a versa. But ultimately they arrive one of those two places. They
75:31 produce one hormone that one neuron produces one Norma, and it responds to
75:36 signals that it produces are too content produce. Um, the anterior.
75:44 , um I don't know if I get to this. So what What
75:47 the two hormone? Few vasopressin regulates pressure. All right. It regulates
75:52 amount of fluids that you're gonna All right. Ox intestine regulates
75:59 So you primarily think of it in of labor and delivery. But it's
76:02 in multiple other places as well. pituitary. Okay. There's the front
76:09 . Said it produces six different Some of these air called the Tropic
76:13 trophic. Either way, depending on you read hormones when you see that
76:19 traffic it means to regulate something So terrific hormone regulates other hormones.
76:25 thereof. All right, so these include growth hormone, thyroid stimulating
76:32 adrenal cortical, traffic hormone, follicle hormone and igniting hormone, which those
76:38 two collectively referred to the canal trope so you can see regulates the go
76:43 hormones. And then we have the one, which is prolactin. That's
76:47 the PRL is all right now. , they're regulated by one of two
76:53 . They're regulated by hormones that are in the hypothalamus, or they're regulated
76:57 the targets tissue. All right, in other words, what they're doing
77:02 they're telling another tissue to produce a , and that hormone is gonna come
77:06 . And it's going to tell the produce pituitary, whether to produce more
77:13 down regulate now in terms of their of the anterior pituitary. Nearly
77:19 these hormones are going to control metabolism or reproduction. All right,
77:26 you think into your pituitary, if can think about getting bigger,
77:31 so that's growing metabolism also getting and reproduction. All right, all the
77:37 stuff in life eating and sex It's . You can smell it. The
77:43 we look forward to, that's why live. Yeah, all right.
77:51 just it's I'm gonna go ahead and every every picture seen Looks like
77:57 But every anterior pituitary I've seen is big. So it's really hard to
78:01 . I put my fingers together. like, the size of little tiny
78:05 . They're small, small structures. usually it's kind of a shape because
78:13 have that pointing out like that. , it's very follicle. So I'm
78:19 is he just sticks out like you know? And also helps.
78:25 reproduction. All right, so and you can just say it's bigger.
78:32 . Why not? I'm gonna ask Discover that's that is anatomy class.
78:37 the good news. All right, , uh, one poor killed.
78:41 hormones are gonna have regulation from hype the set. Are hackers breaking a
78:46 ? That's prolactin and growth hormone. have an inhibiting hormone and releasing
78:49 All the other ones have releasing hormones the hype elements, and they're only
78:54 by their downstream targets. And so so that you have an idea of
78:58 , this is kind of stuff functions . You can see prolactin low production
79:03 says the name crow for lacking for Making milk after station LHC regulate the
79:09 nads as I mentioned thyroid stimulating What do you think? It stimulates
79:15 fire. And you see how you this, kids after while you're
79:17 Oh, you know, a see adrenal cortical tropic korma, the adrenal
79:24 . Okay. And lastly, growth . What do you think growth hormone
79:30 regulates growth, but it's not actually because it is a trophic hormones.
79:37 right, so it regulates the hormones a liver. All right, So
79:42 in the hyper salivation. Yes, am washing the clock. I know
79:45 guys are desperate to get out of , but let's face it, you're
79:47 go home and sit in a Anyway, this is your only contact
79:50 humans. So you know, we'll as much fun as we can while
79:54 here. All right, so these the hormones of the pair gland you
79:59 see in the middle right here. are our hormones that we're looking
80:03 It tells you what type of cells that each of the cells are called
80:07 , so the first half of their just tells you the type of hormone
80:10 producing. And then on the far of the chart, you can see
80:13 the left hand side those air the right? Those with releasing hormones you
80:18 see growth hormone releasing hormone diarrhea, Releasing Home Quarter Co. Tropic Releasing
80:23 Gonadotropin Releasing Hormone Notice From the High We have releasing hormones and I did
80:28 it both pro lack and growth hormones inhibiting hormone as well. All
80:33 so we're regulated through the hypothalamus. then that signal causes the anterior pituitary
80:39 release its specific hormone. That specific then goes down to the target
80:44 And what we have is something that like this good, Really. This
80:49 the very thing you see here is battlements. There's your anterior pituitary.
80:53 your target tissue. And so the is gonna produce a hormone that regulates
80:59 hormone in the anterior pituitary that caused release of that tropic hormone, which
81:03 its target tissue, which causes the of that particular hormone that you're trying
81:10 get produced and what that hormone does it has some sort of function that
81:14 not gonna worry about right now. we're worried about is how we regulate
81:18 . See, when I produced recently the side, when I produced the
81:21 C. T H, which is anterior pituitary hormone, not only does
81:26 cause production of the cortisol, it accident negative feedback back to the hype
81:31 balance. It says you told me make a C T h. I
81:34 made a c t. H here am. So stop telling me to
81:37 a C T h. That's a feedback loop. All right, that's
81:42 short loop. And then the long is the opposite, right? The
81:47 down the bottom goes back up to to the anterior pituitary. This is
81:53 short loop. It says, you told to make cord is all
81:57 here. Stop making a C th the anterior. Pituitary does a negative
82:01 , but it also acts in the loop feedback back to the hypothalamus.
82:08 if that I promise that says, the cortisol that the long pathway told
82:13 told to make stop making crh so I don't make a see th so
82:20 don't make the quarters all and you the signal. And so, by
82:25 the signal happens to the cortisol levels time drop. And when you no
82:30 have that inhibitor, then the CRH up with cousin production of a C
82:35 . H, which causes the productive . So you could see what we're
82:38 here is we're going back and forth and over in a very pulse little
82:43 . There's also something called a very feedback loop. If you ever see
82:46 , we're gonna talk about it. it actually is even shorter than it's
82:50 in the organ. It's so this where we're going to stop because I'm
82:54 slower and I'm already waivable way, behind. All right. But what
82:58 want to do that I want to open up for questions. This is
83:01 . I'm used an example of here cortisol. But this is true for
83:04 of the hormone we just looked at are produced in the anterior pituitary.
83:07 should know highlight balance, What it's . And here, Pituitary. What
83:14 is producing in response to and what downstream hormone is all right. I'm
83:20 gonna ask what that hormone does. When we get there, we'll get
83:25 . Any questions? Just give me heck out of here. Because,
83:30 know, track is gonna be terrible there. What with it? Everybody
83:33 home. I mean, I love right now. Man is awesome.
83:39 know, I don't think I've gone than 90 miles an hour.
83:45 Oh, yeah. That's true. have construction on 2 88 so I
83:50 to. Alright, guys, that's . When we come back, we're
83:53 to We're going to introduce ourselves to activity. Um, and we're going
83:59 use an analogy to help us. understand it. I want you to
84:02 really, really hard about ST um, high school that sits right
84:07 to Lamar High School. You have think about it all, but that's
84:11 be my starting example. Like what hell is this been in Houston?
84:15 enough? You know where those two are for it? No other questions
84:26 the gallery. All right, stop
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