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BIOL 3324 Human Physiology - 3324_lecture04_0901
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00:05 Well, I'd like to thank you for making it today, avoiding the
00:10 strike. Yeah, I I am suffering just like you are walking over
00:18 , there's a huge puddle of I said I'm not stepping in
00:20 So I went right into the grass the water there was even deeper.
00:26 I'm walking around with a wet foot a wet sock. It just
00:30 But anyway um Yeah, this is I know it's hard getting into a
00:35 when it's like crappy outside and so glad you all made it. And
00:39 you're looking at up here is something not in your slide, you probably
00:42 a white or clear sheet. If you can write something like this down
00:47 draw this out. And really the I show you this is that it
00:50 make the understanding of how receptors work in a very general sense, what
00:58 looking at is a pathway or it's different types of pathways merged together.
01:05 help you understand that. It doesn't what type of receptor you're looking
01:10 They all use the same mechanisms sort . Okay, and so very often
01:17 we'll do is we'll sit there and to memorize. I'm gonna memorize this
01:22 . I'm gonna memorize that pathway. gonna see what this receptor doesn't see
01:25 that receptor does and while it's important very specific conditions are very specific
01:31 If you see a receptor for the first time that you've never seen
01:35 If you understand this, you already what's going on. All right and
01:39 looking at this. Okay, there's a bunch of triangles and circles
01:42 squares up there. So, what they all mean? So, let's
01:44 through it. What we have up , L stands for ligand ligand is
01:51 a molecule that binds to a So, that's why it's called a
01:55 . Alright, the R is a we're keeping it. Simple receptor.
02:03 , so, there's a receptor. stands for transducer whenever you see an
02:07 behind a letter, usually in one these maps, what that usually indicates
02:11 something that was turned on is now . All right. And so sometimes
02:15 might see the the asterix here and no asterix there. So, that's
02:19 you something that was turned on was off. Okay. And then over
02:23 the easy stands for enzyme and we're easy to distinguish it from E.
02:29 . Which is effect er what does effect er do causes the effect?
02:35 right. And then what we have here is the number two, the
02:37 two stands for second messenger, second . So, all right.
02:44 what you can see here, is in a very general sense, we're
02:49 have Liggins that bind to receptors because what Liggins do. And when receptors
02:52 activated, they change the behavior of molecule within that membrane or within
03:00 All right. So what is it going to do? Is it always
03:03 to have a transducer? The transducer be part of the receptor, but
03:07 is turning the external signal into an signal transducer. The signal. And
03:13 what's going on here. All Usually that trans that trans deduction results
03:19 the activation of some sort of Alright, and then that enzyme,
03:26 may work through a second messenger to an effect er or what it may
03:30 is it may activate another enzyme which another enzyme, which activates another enzyme
03:35 on and so on and so on so on and so on and so
03:37 . Forever and ever. Until you down to some sort of effect.
03:41 All right. So, when you at a system, all you gotta
03:44 is ask yourself, Alright, if looking at a receptor here, what's
03:47 ligand? Okay, great. What's activating? Is it working through a
03:52 ? Is it a transducer itself? is the next molecule in the sequence
03:55 be? What enzyme is next And once you see that, then ask
04:00 question Or is it a second No. And if it's a second
04:04 . Okay, what is the second do? Does it act directly on
04:07 effect er or does it activate a cascade? And then you can learn
04:11 signaling cascade if you need to. right. How many guys have taken
04:14 molecular biology of the cell biology Alright. Did you guys learn about
04:19 ? What does activate You wanna know , canes, canes. Right.
04:30 , you're right, it's napkins. the thing that activates map kinase kinase
04:35 what activates map map kinase kinase kinase , which is activated by matt cain
04:42 cain cain cain which is activated by cain cain cain cain cain cain
04:48 You see how original we are in ? Yeah, these systems become very
04:55 simplified once you start seeing the pattern nomenclature and the pattern of activation and
05:05 . So, what we're gonna do is we're gonna literally sprint through a
05:08 bunch of these. I'm just gonna them. And you're gonna start seeing
05:10 pattern. Okay. The first one nothing to do with the ones the
05:15 I just showed you this is the type of receptor system that we
05:19 All right. And the example that using is using at the level of
05:22 neuron. But what we have is a neuron. We can see that
05:25 releasing some sort of ligand that ligand binding to its receptor. The receptor
05:29 happens to be a receptor channel. . Or or an ion channel.
05:34 so what happens is is you basically a chemical receptor or chemical li gated
05:41 . So, when the chemical binds the channel, the channel opens up
05:45 ions start pouring through and we've changed activity of the cell by changing the
05:50 of ions or the charge inside the ? All right. We're gonna see
05:54 over and over and over again. is like the simple one that everyone
05:57 . It's not a hard one to because you can envision taking a key
06:01 putting it in the door and opening door and the door opening as a
06:03 of putting in the key. That's that's doing. How long does the
06:07 stay open? As long as that is bound up? So you're gonna
06:12 things that are gonna force that thing close. Right, gonna chew up
06:16 key in other words. How long the doors stay unlocked? As long
06:19 you have the key in? So out the key. The door becomes
06:22 again. Does this one seem You're looking at me like I don't
06:27 . I can barely see anybody else being blinded by the light?
06:32 Does that make sense? I mean confident about? Does that make
06:34 Yes or no? Yes. You ready for going back to the
06:38 ? The normal thing that I just you. Here's our first one G
06:43 coupled receptors There are roughly 4500 G coupled receptors in the human body.
06:49 4200 of them are found in the . This is how you can tell
06:54 difference between a strawberry and a Right, so what's the G protein
07:01 receptor? You can see it has specific feature to it. Seven trans
07:05 regions. You've probably seen these before there called G protein coupled receptors because
07:11 are coupled to G proteins. G proteins are this very very scary
07:17 . Hetero trim eric meaning it has parts and all three parts are different
07:20 each other. All right. And that combination this protein which has an
07:25 beta and gamma sub unit is shown here and basically what it is,
07:30 beta gamma subunit helps to stabilize the subunit. The alpha subunit binds up
07:35 . T. P. And converts into G. D. P.
07:38 if it converts a GTP and GDP where the G protein portion comes
07:42 But what do we do when we we catalyze the reaction? What are
07:47 ? What type of molecule are we ? C. Yeah we're all
07:52 So this is a kind of And the thing that keeps the enzyme
07:56 doing stuff is that beta gamma but alpha part is an enzyme and it
08:00 as that G. T. A. S. Alright so it
08:04 G. T. P. S . That's what that little circle is
08:07 to show you. So what we is when we bind to a G
08:11 we're gonna activate this alpha subunit by changing its confirmation. It's gonna kick
08:17 the beta gamma. The alpha subunits . Alright let me go find something
08:20 turn on. It's kind of like seventies. Thank you for laughing and
08:26 to the rest of y'all suck, teasing. You don't suck. You're
08:31 disappointing. So let's take a look this. Oh look here's something from
08:36 book notice they don't have names of . What do they have? E
08:42 ? What do you think enzyme So here we have Lincoln binding the
08:46 , here's your G protein, G becomes activated. See I've activated it
08:50 it's like all excited and starry. so what is it gonna do?
08:54 separates it binds to the first the first enzyme that activates and does
09:00 . We don't know what it It just so happens that beta gamma
09:04 discovered much later. I mean we've for years but after they discovered that
09:08 oh beta gamma does stuff to, actually activates its own enzyme and it
09:13 stuff. So if you went back looked at this thing, what you
09:16 is alright, my transducer here would the G protein. What am I
09:22 ? I don't know, it depends which system I'm looking at.
09:26 so in this particular example we have things that we're activating downstream from the
09:32 but we don't know what it One is just being done by
09:35 that's gonna be the one transaction, second one's gonna be by beta
09:40 Here's something a little bit more Using the G protein coupled receptor.
09:44 here, what we have is the protein here, we see it
09:47 activating an enzyme Our enzyme here is Admiral cyclists. Now this is the
09:53 most common type of G protein that gonna see. Or G protein activation
09:58 we're going to see in the Alright, So the G protein and
10:02 should point out just as an not for you to know, but
10:05 see a little sub symbol right That? S right. That's just
10:09 of several dozens of different subtypes of alpha unit. Alright. There's G
10:17 or or alpha not alpha I. S. S stands for stimulation.
10:22 stands for inhibition. And then there's whole bunch of other ones.
10:26 but what you can see here is activating an enzyme. This enzyme is
10:32 a second messenger. The second messenger going to activate our effect. Er
10:39 right, so this is typically referred as a cyclic A. M.
10:43 . Admiral cyclists. Or the cyclic . M. P. P.
10:46 . A. Pathway. Alright. you'll see this over and over and
10:50 again. And if you don't know cyclic GMP is. It's just a
10:54 a teepee that has been converted. chopped off the first two phosphates and
10:59 we bent it around and rebound it that we create a little tiny
11:04 You know, circular circular bond. , that's the difference. It's not
11:09 it's not adenosine mono phosphate. What gonna do now? It's cyclic adenosine
11:16 cyclic GMP. So what does it ? All right. Well psycho KMP
11:24 P. K. A. By binding up a portion of the
11:28 K. And releasing the activation So there's basically a restrictive or regulatory
11:35 that says P. K. You do anything until you've been activated.
11:38 that's what that role of psycho KMP . And so you can see here
11:43 the catalytic subunit goes and activates something which goes activate something else goes activate
11:47 else. But now this right here a is our effect er it creates
11:52 effect in the cell. And what P. K. Do? It
11:55 do dozens of things. It can on some molecules that become transcription
11:59 It can turn on pathways that are existing in the cell and activating them
12:03 that the cell is becomes functional or . It can actually turn things
12:08 I mean there's all sorts of of that can occur as a result of
12:13 activation of P. K. So why we call it the defector.
12:18 right. Does this look any different what we just saw? No.
12:23 . So what do we have We have our receptor here. We
12:27 our G. Protein. What's our . Actually it's not but that's a
12:32 guess. Right. Because it's showing because the actually what we're looking at
12:36 and I'm not trying to be I got them know what I'm showing
12:40 here is a system that works inside eye. And what's unique is that
12:46 ligand is already pre bound to the . We just don't show it in
12:49 picture. What happens is light hits ligand and changes its shape, which
12:54 the receptor which changes the activity. you're right to think wait, light
12:59 the activator here because it's activating the of the ligand. Alright, but
13:05 you're thinking right, It's like, a second. That shows me.
13:07 showed me the picture. Where was up here? And you're right in
13:10 sense. This is the activation. you can see here here's our
13:16 Our enzyme is phosphor diasporas PDE. lots of different Pds in the body
13:22 in this particular case PDE is responsible taking a cyclic molecule cyclic GMP.
13:29 ? Which looks like cyclic GMP. it's a guanine, guanine up
13:32 The whole thing is iguana scene. right. And it turns it into
13:36 . So, basically takes that bent and pops it so that it's nice
13:39 simple. And then that becomes it's not really a second messenger.
13:45 it is is you're depleting the presence the second messenger. This activator.
13:50 that then what happens is is a that is normally open by the presence
13:54 that now closed. So, you it's kind of a different effect.
13:58 are the steps very similar, Its ligand receptor transducer enzyme. Something
14:08 . Alright, creates an effect and would be the effect. Er All
14:15 . Does this look scarier and I like the shaking of the
14:19 No, that's not scary. ma'am. Mhm. In this case
14:24 don't see it. It's not shown . It's it's light. It's affecting
14:28 . That's already pre bound, but showing you activation. Right. And
14:32 the idea. Alright, so, one here you can see the
14:37 See when you see the lights Did you hear that sound? All
14:44 . What's this? What's that? protein which is a transducer? What's
14:51 activate enzyme? This enzyme is phosphorus pay. See if you have a
14:57 like a C. Do you think have a phosphor like baby? What
15:01 an A. Yeah. And this actually fossil C beta. Oh,
15:06 . That means there's a fossil like C alpha. Yes, is there
15:10 gamma Probably. Alright, so part this is it's just kind of recognizing
15:15 patterns. Right. All right, look what we have here, we've
15:18 ligand receptor transducer enzyme. And what enzymes do they create second messengers?
15:27 you can see a second messenger? the second messenger doing activating and
15:33 Er All right, now this effect happens to be another kinase protein kinase
15:39 . Now please do not memorize all , I'm not gonna ask you every
15:42 solitary step here. Right, but you have a protein kinase C.
15:45 do you have? Do you have kinase B. What about an
15:48 Yeah, we already saw that didn't we? Okay now look here
15:53 is where I had fun with you the other day. Right? I
15:55 hey remember those fossil lipids? I you not to memorize but memorize this
15:58 . But don't memorize it. Remember which one was it? You
16:05 ? Foster title on a Seattle That's just a tough one. Right
16:11 look what we got here. It foster Foster title and hospital is cleaved
16:18 it forms I. P three and . A. G. And again
16:22 don't need an advice. Triglyceride. I don't care. Anyway. Now
16:29 created another molecule so we're acting through create our second messenger. Second messenger
16:34 one thing. Here's another second messenger to an acting on a channel causing
16:41 channel open up which releases calcium, now acts as a second messenger.
16:47 what we've done now and just just you how it how it becomes?
16:51 expansive. Is that a pathway like isn't just a you know a series
16:56 playing the game mouse trap. Do guys ever play that game? I
16:59 think anyone ever played the game. think if you had the game you
17:02 built the mousetrap thing and just wanted hit the marble to see the whole
17:05 Goldberg thing going on. Right. what I did. Right. That's
17:10 not that's not what this is is a step A to step B to
17:13 C two, step two, step . Right? It may be all
17:16 things but along the way there might a step B one and B two
17:21 B one is turning on C. and C. Two and B two
17:24 turning on C. Three and Four. And all of a sudden
17:28 you're turning on multiple pathways at the time. Alright, so using these
17:35 of pathways allows you to do a bunch of different things and that's what
17:37 one is trying to show you, that I'm not just turning this
17:42 I'm turning this on as well and when this gets turned on its an
17:46 that's gonna act on multiple things. when this calcium gets released it acts
17:49 multiple things. And so I'm creating massive cascade of events calcium tends to
17:57 to and this is something you should , just like calc cyclic GMP binds
18:00 protein kinase. A calcium binds to molecule called cal module in and he
18:06 in the name what it does cal calcium mod moderate modulate. And I
18:12 comes from protein cal modular. So calcium binds can modulate modulate serves as
18:18 effect er it causes an effect. wherever you see cal modulate must be
18:22 something. So here we see cal binding to an inactive protein and it
18:27 it active now. What's it Who cares in this picture?
18:31 But when you see that this is second most common type of pathway through
18:37 g protein coupled receptor. Alright so see a calcium cal modular system or
18:43 might see a cyclic A. P. P. K. System
18:46 understanding oh I'm not gonna be confused receptor receptor transducer transducer to enzyme enzyme
18:53 probably a second messenger if it doesn't something else and then that second messenger
18:59 an effect. Er And it may a pathway There's a scary looking
19:05 Or is it which side do you to start on left? Okay.
19:10 what do you got up there Ligon enzyme enzyme makes second messenger. And
19:23 at what the second messenger it activates . What does the activator do activates
19:28 enzyme? All right. And so can see part of that, remember
19:32 I. P. Three? What the things that it does is activates
19:36 opens up a channel which releases calcium you can actually stimulate this. What
19:40 stimulates all this fun stuff of making the different types of Luca trains and
19:45 cyclones and all the other fun stuff you may or may not have ever
19:49 of? Have you ever heard of lipid signal ear's I'm sure you know
19:53 prostaglandins? Prostaglandins. Okay prostaglandins are um uh lipid signaling molecules that are
20:03 for contractions in the body like labor right on the let down reflex when
20:10 breastfeeding. Some of the fun ones . Prostaglandins play a major role in
20:17 um some other ones that you mean heard of, have you heard of
20:20 throne boxing's? Okay, that's From boxing thrombosis, what does that
20:26 of sound like to you guys thrombosis has to do with what blocking blood
20:34 ? All right, good. I mean you're pointing. I understood
20:37 unfortunately can't do that on exam but the this thing sorry but it basically
20:44 with blood clotting. So throwing boxing and a signaling molecule that plays a
20:50 in clotting um Luca trying what do think? They play a role in
20:57 sites and inflammation and immune response. , so these are just a class
21:02 of molecules that are being regulated through process up here and you can start
21:08 one side and go through one enzyme you can start on the other side
21:12 go through another enzyme, interesting. I just have to have the right
21:17 depending on which signal is activated that's to create this pathway. And again
21:22 glad I don't see anyone writing this down because I'm not gonna ask you
21:24 is the pathway to produce, you throwing boxing A. Two thank
21:30 Alright. Yeah. Yeah. Absolutely because I'm gonna show you something
21:38 in just a second. All Oh I'm here. So here's an
21:44 of not a G protein. what we're looking at here are the
21:49 receptors. Now what's unique about these receptors is they still have a receptor
21:55 instead of having to have an enzyme a transducer downstream we have the enzyme
22:02 associated with the receptor. Okay, what do you expect down stream of
22:06 enzyme, what do you expect? an effect. Er And if it's
22:13 directly in effect or what would it do you think? Second messenger or
22:18 enzyme? Alright. An enzyme turning another enzyme which turning on another enzyme
22:22 on and so forth. Alright, typically these types of receptors have to
22:28 a dime. Er So I think have one in here. That's
22:31 I can't see which one it Um nope I thought insulin was gonna
22:34 on this one. But I mean heard of growth hormone right, so
22:38 an example, there's growth hormone itself you need to have to growth hormone
22:42 come together to bind that and then gonna activate an associated enzyme. This
22:48 doesn't actually have the enzyme as part it. So the jack system here
22:52 part of an association here um what can see on the N.
22:57 F receptor or here on the G. F beta. Those are
23:01 that are that are enzymatic but again principle have to have two of
23:05 11 leg in two receptors that come that activates the system. You can't
23:10 activate one kind of like a kit . You have to have both.
23:16 my goodness, scary. Look at . And it has abbreviations like Mech
23:21 there's that map K. And there's . O. S. I can't
23:25 the son of, I can't even . It's just they're awful awful abbreviation
23:31 alphabet soup of molecular biology. But this really that hard? What do
23:37 got Liggins? What do we Right here, we can see our
23:43 . So our enzyme is activating. I if you see something else attached
23:48 it's usually the enzyme. So enzyme an enzyme which activates an enzyme which
23:54 . What do you think? What you think that is enzyme which activates
23:58 which activates if you don't know Is kindness activates a which does something
24:07 ? Er Right down here, what's gonna be transcription factor? So transcription
24:14 is changing the the expression of genes that would be an effect.
24:23 So what do we got ligand enzyme cascade of enzymes at the very
24:30 effect? Er Yeah, we know today it doesn't matter. That's the
24:39 news. Right. For us, not gonna give you a path
24:42 What is this? You know? not the point. The idea here
24:46 all right. How many you guys taking the indo class. Endocrinology.
24:51 , I'm gonna make your life You're gonna learn everything you need to
24:53 today for that class. All And I'm just gonna you're gonna just
24:59 there for the rest of the class Really okay, now, it's just
25:02 memorizing which one each one does. right. How many guys are taking
25:05 cell bio class now? Right. took it before. Does this stuff
25:10 familiar to you? Yeah, this is what cell biology is learning
25:14 these pathways do. Right. the idea here is now, what
25:18 doing is we're putting ourselves in a where it's not I'm memorizing a specific
25:23 . I'm understanding the concept of this pathway. Once I understand a receptor
25:30 , it doesn't matter what I throw you, you should be able to
25:33 at that. Oh, well, thing is binding a receptor. What
25:37 the receptor do it is what's turning inside signal, you know, or
25:41 to an outside signal. So, can create an inside signal. What
25:44 an enzyme do it catalyzing a reaction in one of these pathways.
25:49 that kinda makes sense. So, idea here is being able to
25:52 you know, kind of, if looking at a pathway, can I
25:55 a sense of what's going on in ? Yeah. So, in this
26:01 one, I would say no. and the reason I would say,
26:05 mean, you might say that Wrasse be considered one. So Wrasse there's
26:12 and wrap and then the G proteins they're all GTP aces. But because
26:17 G protein coupled receptors directly with the protein, it kind of gets a
26:21 consideration. Could have been known But is it any different than rasa
26:25 ? Not really. And so why is called a transducer one is is
26:30 considering enzyme just probably has to do its location. All right. And
26:34 that's kind of a nuanced thing. like well um I've seen if I
26:38 back here and I apologize because this making me pause. I've seen people
26:42 refer to this as second messenger, I've seen it referred to a second
26:47 . So it's not a it's not hard and fast rule. This is
26:50 something that you're memorizing so that you go okay, um this is a
26:54 messenger and this is not this is of a do I understand what's coming
27:00 here? What is the goal? is the outcome of this molecule?
27:04 it catalyzing a reaction or is it on a catalyst? Right. It's
27:09 on a catalyst or creating some sort an effect then it man, I
27:14 I wouldn't let students standing out there it happened. Um It's it's kind
27:19 defining what its behavior is, That's what you're really kind of doing
27:23 right, there's another group of And again, when you start looking
27:31 this, they start falling into place quickly. Right? So here's your
27:34 protein coupled receptor, right? And we're doing now is we're saying all
27:38 , we're not gonna we're not uh the question, what's it doing with
27:42 that are already there? Were asking does it affect gene expression? Because
27:46 can change the activity of the cell playing with the machinery that's already
27:50 So like think of this room in room, There's already wires and switches
27:55 stuff that go to these lights. so I got to do is just
27:57 up to the light switch and turn on and turn it off.
28:00 So everything that I need to do change the brightness of the room exists
28:04 in this room. Right? But expression says no, I want to
28:08 the light in the room. So have to wire the room and build
28:12 lights and put everything in. I've got to make everything in order
28:15 there to be changed. But I change the activity. Right? And
28:20 kind of what this is. there's single transaction that can be used
28:23 activate transcription. Can I time out a second just to be 100%
28:30 I usually talk and you'll hear most us talk in the affirmative turning
28:35 Gene expression turning on, you a cascade. The opposite is true
28:41 well. I can turn off gene , I can turn off the
28:45 it's just we tend not to talk that. Right? So I could
28:51 a gene or I could be activating system that basically says you're not allowed
28:55 go so just know that that can all right now, in this particular
29:01 , this is a system we've already right, what's that molecule right
29:04 it says right next to it, protein kind of say. So you
29:08 see it acts through the second messenger GMP. There's those catalytic subunits they
29:14 in and they activate the transcription factors that you can read the gene.
29:19 . And we're putting it right beside jak stat pathway. Alright. And
29:23 jak stat pathways, what we're doing we're activating stats that becomes phosphoric is
29:29 and goes in and it serves as transcription factor along with other molecules and
29:35 what it's showing here as well. . Just using different receptors. So
29:40 on what is that? Gamma there's alpha. You ever felt a key
29:44 you get the flu blame that molecule there, just as an aside it
29:52 these systems that say, you basically telling all the cells hey you've
29:57 infected so tell everybody else you've been and all the cells go. I
30:02 . So. Alright, but do see pathways are are very similar.
30:07 doesn't matter if it's this longer stranger or it's a simple one where it
30:11 locates on its own so far so . Alright. So in all these
30:18 that I just showed you what we're at is we're looking at systems where
30:22 a signaling molecule outside the cell that to a receptor. So that signaling
30:28 that we're describing up here has to um water soluble. All right.
30:35 in all these cases we're really just about water soluble signaling, right?
30:40 what happens when we have something that's soluble? Well, that's when we
30:44 across the nuclear receptors. All right , the nuclear receptor is not gonna
30:49 limited by the presence of the fossil bi layer, the lipid bi layer
30:55 . It actually hates the watery environment the cell. It hates the watery
31:00 inside the cell. And really the way to say is the watery environments
31:03 the little molecule. And so it's get out of here and it's like
31:06 trying I'm trying but I can't go . Right? And the truth is
31:11 most of the time when you were about these things, what we're not
31:13 you are the chaperones. And so are chaperones that basically sit there like
31:18 , oh you're such a cute little , let me let me hide you
31:22 the water and I'll carry you in blood and I'll protect you and then
31:27 well I'm no longer interested in you now I'm interested in you again.
31:30 no, I'm not. And so molecule falls back and forth between the
31:34 states and the same thing is going inside the cell. But we ignore
31:37 just for the sake of keeping things . Alright so nuclear receptors can be
31:46 in the nucleus because duh right says the name nuclear receptors but they can
31:51 trans locate to the cytoplasm. They in both environments equally. But when
31:57 get bound up by their ligand then they're gonna do is they're going to
32:01 locate to the nucleus and here they're to serve as a transcription factor.
32:08 . Typically what's gonna happen is is when you bind that nuclear receptor.
32:13 here you can see you get In fact if you don't get demonization
32:18 you don't get activation of the transcription on. It's kind of like the
32:24 chinese receptors that we just saw you have to have two of them
32:27 order to get activation. It's kind the same thing. You have to
32:29 two molecules here they come together once come together it's like now we can
32:33 what we need to do. And what they do is they recognize a
32:37 specific region of the description factor which the transcription of the gene or it
32:46 inhibit as well just depends on the but we're just gonna go ahead and
32:51 activation for right now. So have totally confused you at this point?
32:57 . No. Yes I have. right. No I know you go
33:00 . Demonization means two things coming together creating one thing out of two.
33:06 so I'm gonna now challenge you since actually asked me a question. What
33:10 you think a hetero dime er is to differently? You answered for her
33:16 that's good. Alright. Now her what's a home a timer two of
33:23 same coming together. Right. And there are hetero timers that can be
33:27 and homo dimmers and again this falls to that cascade of stuff that you
33:32 to learn cell biology and whatever we're gonna worry about it right. But
33:37 idea here is so when I see receptor, what do I know?
33:41 nuclear receptor can be out in the is all or it can be in
33:44 nucleus it's not doing anything until it bound up. When it's bound up
33:48 goes into the nucleus it has to memorize and once it did memorizes it
33:52 as a transcription factor binds the N. A. Serves as that
33:57 factor that promote the production of that or inhibit right nuclear receptors always happening
34:08 the so where they bind it can occur in both places now. Typically
34:14 we say is that it's gonna occur here because again those those hormones those
34:20 or anything that that's that's lipid soluble not going to want to be out
34:26 that. Also there's usually some sort carrier molecule that's helping it along in
34:31 case it's not showing it to But what it does basically binds it
34:34 and hides it or sequesters it from watery environment. And so kind of
34:39 it is is like I'm handing it to the receptor and so those larger
34:44 don't really trans locate back and forth the nucleus. Only the receptors
34:50 So typically what you'll see is that bind up and then once they're bound
34:53 they go zipping down into the That's a typical thing now. Is
34:58 100% true. No, nothing in is 100% true. Right.
35:03 I just want to say again, license again. Probably because I copied
35:09 pasted it. Let me see, me see. Uh which which over
35:17 or over here? Let's see, is lipid soluble o on the previous
35:23 . Oh, so over here, . So here, this is the
35:27 of where we're binding receptors that are in the membrane. So that ligand
35:33 penetrate through the membrane, there is nuclear receptor for it. So what
35:36 doing is I'm getting transcription as a of moving through that cascading event.
35:42 . I'm activating something to go down act as a transcription factor. I'm
35:47 activating the transcription transcription factor directly over . That Ligon can come through the
35:54 , there is no receptor up there for the big time out. So
36:03 was like dogma for years and years years. And then about 30 years
36:06 someone discovered like, oh look there's membrane bound estrogen receptor, oh
36:12 there's a membrane around progesterone receptor and they just screwed everything up for the
36:17 of us. In fact, you that big building over there by
36:21 the the nuclear receptor center or center nuclear receptor research, Guess what they
36:27 over there, That stupid stuff. , exactly. But anyway, so
36:33 point is, is that what we're at now? And I see the
36:36 , my point here is that the doesn't have a receptor in the plasma
36:41 . The lipid, the lipid soluble can pass through that just fine over
36:49 , the water soluble ligand cannot it needs to have that trans membrane
36:55 in order to activate some molecule down . Does that does that make a
37:00 bit clear? That is correct. , yep, I'm about to make
37:08 life easy for indo okay, you're to see this in a couple of
37:12 , you're just gonna be like Yeah, once you learn it's just
37:16 everything else, just put it in put in its basket and move
37:20 Yeah, and I'm sorry, I her first, I apologize,
37:27 Mhm. Results for the 2nd look . So what it's doing is trying
37:42 find and it's basically being excluded by water. So remember the polar heads
37:46 not co violently linked and you can through them. It's just where does
37:51 thing settle? Where does that lipid ? Right. And so it's not
37:55 settle in a watery environment because the says get out of here. I
37:57 like you. And so it's trying find a lipid environment to settle
38:03 All right? But because we have these carriers and other things that we're
38:07 showing you, it doesn't settle in membrane. It actually gets pulled and
38:11 held by that carrier. Yeah. or not. Oh my goodness,
38:20 right ahead. You get the other star. I'm sorry. We all
38:24 gold stars for just showing up from rain and the lightning. So you
38:27 two gold stars. No, just stars. Yeah, you should go
38:31 go home, go to amazon. your little packet of gold stars when
38:35 come home just slap one on your . Alright. But yes,
38:39 and we're gonna see there's actually a in there as well. But
38:42 that is true. So peptides typically Almost 100% knows how I'm not going
38:48 commit to 100% because I know the I walk out of here, someone's
38:51 but dr wayne. I've been working this lab and this is what we're
38:54 and it's not and I'm just alright look, there are rules and
38:58 there are exceptions. So we learn rules and then when we have to
39:01 learn the exceptions. Okay. But peptides and proteins are water soluble,
39:07 they're gonna use which type of receptors bound and then lipid soluble ones typically
39:15 which type of receptors nuclear. Except for that stupid ones that they
39:20 about 20 years ago, that just everything up and makes my life
39:24 Oh, the other thing I want point out here because we're dealing with
39:29 , the effect of a lipid soluble acting on its receptor. The result
39:36 uh delayed. Alright, so think a series of dominoes already stacked
39:41 If I press the first domino, falls down, I get a quick
39:45 that last domino falls fairly quickly. ? If I have to stack the
39:50 first before I push them down, what this is kind of like just
39:55 trying to say if I want to the room bright and I have to
39:57 the electrical system, it's gonna take little bit of time before you get
40:01 know, get the room light and kind of what you're doing in this
40:04 of system. But as a result types of systems last longer. So
40:09 effect of a ligand binding its receptor increasing transcription is a delayed effect,
40:16 a longer lasting effect when you're dealing a system where you're dealing through a
40:23 , a signaling cascade, you get very quick response and it's a very
40:26 lived response. Just as an So some of the work that I
40:30 to do was I would add hormone cells in a dish. And my
40:36 time point was always like 30 So it's like literally you add all
40:39 agents and then you take the first out and you freeze it so that
40:42 reaction would stop. That's my first point was 30 seconds and I can
40:46 see a response and then that response continue getting bigger and bigger and bigger
40:51 you know about, Oh, I know, 2012, hours. And
40:54 after that it falls down. All . Oh yeah, it was
40:58 I mean you go like 30 a minute, five minutes, 10
41:02 , 30 minutes. So you're sitting going in the middle of the night
41:09 off you go again. Yeah, is fun folks. Alright. But
41:15 it's a very very quick response and cascades or falls off fairly quickly.
41:20 I throw this up here because I a chart like this is one of
41:23 best ways to start learning about your types of receptor types. It just
41:29 you different types of characteristics and it let me compare and contrast these two
41:34 . What do what type of ligand gonna buy into a member. What
41:37 of ligand binds and nuclear, you what is the permeability and so on
41:40 so on. And so once you that you can kind of start
41:43 oh here's a pattern. So if know what the ligand is and I
41:47 what type of molecule is, I know what kind of behavior I can
41:51 from it, right? And that's of what the next stuff is all
41:56 . You know, good time. , Alright, so I'm doing pretty
42:02 . We're gonna probably in on time , I'm gonna end everything, it's
42:05 be awesome. And now that I've that I'm gonna miss the last 15
42:12 . So what is a hormone e sorry, what is a hormone?
42:18 if you haven't seen my big fat wedding one, watch it because it's
42:23 . But one of the characters she to hormones as hormone ease. And
42:26 just sorry, So hormones are basically secreted by a cell or it can
42:32 a group of cells. And what gonna do is you're putting it into
42:35 blood. And so it's going to through the body and it's going that
42:38 hormone that signaling molecule is now traveling a very long distance place to create
42:45 sort of change and that's the target . So the target cell has to
42:49 the proper receptor, if it doesn't the right receptor, it's not going
42:51 respond. And so the cell the just keeps on going by now in
42:58 that definition, which is kind of if you look at any textbook,
43:01 how it describes it. The definition hormone has kind of gotten fuzzier over
43:06 last couple of years. Right? for example, you know, hormones
43:10 can kind of think, oh steroid, that's an easy one.
43:13 , thyroid hormone, growth hormone, say in the name those are hormones
43:16 some of those are those are actually hormones, some of them are
43:20 And so what's a neuro hormone, hormone is simply one that is
43:24 say in the neurons versus say out epithelial cells, which is where other
43:29 come from. And then we got fun ones like the cytokines.
43:33 cytokines were first discovered, you these are immune signaling molecules. And
43:39 they behave very similar to hormones are in the blood. They travel uh
43:44 sometimes, but they are not secreted a gland and they're not secreted from
43:50 neuron, they're secreted from immune So is it a hormone? I
43:57 know, you know, it's it's molecules. So kind of now they're
44:01 of like hormones are a specific class of signaling molecules side of kind or
44:05 one. And so the lines get of blurry All right. So in
44:12 that just when you look at just kind of ask, where is
44:14 being secreted from. Right. So hormones are gonna be secreted into the
44:19 . Alright. That's easy except for hormones. Ecto hormones or those hormones
44:24 are secreted under the surface of the . But what now? Yeah,
44:29 are an example of an ecto And in humans, pheromones aren't that
44:34 of a deal. But in other , pheromones are a huge deal.
44:37 these aren't the only ecto hormones. a lot of communication that takes place
44:42 you took plant biology, right? learn that sells or plants talk to
44:46 other via extra hormones. Alright, kick me in the face. One
44:52 thing to worry about. All Well, the target. Well,
44:57 when we say it travels in the , that's like, okay, what
44:59 means is going to some far off place. Great. Except that sometimes
45:04 releasing the hormone to act on the right next to it. So you're
45:08 with the peregrine response. It's still hormone. So, it's just you've
45:14 to kind of say all right. this is what I expect, but
45:18 is kind of what I'm getting but what is true is that they
45:22 at ridiculously low concentrations. Yeah, basically just into the external environment,
45:35 in that joyous. Isn't that I'm just gonna I guess this falls
45:44 the classification of pheromones, ladies you're be able to smell your child and
45:50 which one's yours and which one is all babies stink. That's that's how
45:57 they all smell poopy but you'll actually able to identify your child by smell
46:03 , ladies in that wild. Um is just another side. We'll get
46:08 it and get to the special Ladies. Your sense of smell is
46:11 million times better than the sense of . And yeah, I mean it's
46:15 proven, oh, colors. We'll we'll talk about colors when we get
46:20 colors. Guys know 12 colors. know all of them, Maybe eight
46:26 . I don't know. Um concentrations we're dealing with very very very
46:32 concentrations um in in these PICO molar animal ranges. And so even though
46:39 have so little hormones circulating in your because of these cascading effects and these
46:44 effects through these pathways that we've already of looked at, you get massive
46:50 . So part of the reason we're , really high on regulating which hormones
46:55 being released is because of the massive that they can produce. All
46:59 so we're talking Peca Moeller Moeller. mean that's PICO. Alright, so
47:09 we're looking at here is I like just throw it up here just so
47:11 can kind of see some reason why take organic chemistry. I know.
47:16 . Yeah, but if you look this, what do you see
47:19 can you can you see the What is that? Yeah. You
47:24 amino acids. It's a peptide? a series of amino acids over and
47:28 again. Right. That And that's peptide. Right. So hormones there
47:34 different ways that we can classify All right. And you can choose
47:38 way that you think is easiest for to understand. I'm gonna tell you
47:41 way I think is the easiest way understand. And then if you don't
47:45 it, you pick one of these ways. All right. So,
47:47 can look at the source of How are these things secreted?
47:51 What is the mechanism of of In other words? What type of
47:54 is it using another? You can at its soluble in water or you
47:59 consider its chemical classes in my The easiest thing is to look at
48:06 because if you know whether something is or something is soluble in water or
48:16 or the other because these are the ones, then you already know all
48:20 behavior stuff. And I'm gonna show this over the next couple of
48:24 And if you agree with me. . Otherwise, just pick one of
48:27 other things because they're all listed You'll just see I think that's the
48:30 way to drop them into a box that's how we learn stuff as we
48:33 things into boxes. Right. So right there. That's cortisol. That
48:38 be an example of a steroid this . Here would be an example of
48:42 amine? You all heard of Right, okay. So then that
48:47 there, that would be an example a peptide. You notice they all
48:51 of have similar shape, kinda just Yeah, I picked those on
48:57 All right. So, we're going first focus on the water soluble
49:05 Alright, so peptides are water soluble like I said, I like to
49:09 in terms of is it water soluble soluble. And so I'm gonna focus
49:13 peptides first. Then I'm gonna focus steroids and then we're gonna deal with
49:16 the Weirdos. I mean, the which can be both. Alright,
49:22 , how are peptides stored? they're proteins. So remember they're gonna
49:25 the membrane systems. That means made the er put to the Golgi cut
49:32 repackage. Put into vesicles and then sit around and wait for a signal
49:36 be released. All right. Because peptides. That means they are water
49:42 . So that means you can store away in a vesicles, which is
49:45 we do. All right. When we synthesize them? Generally speaking,
49:50 kind of this constituency synthesis synthesis. what we can do is we can
49:54 regulate or down regulate synthesis and then can up regulate and down down regulate
49:59 . All right, So, we released out into the blood. So
50:03 we are We've been signaled to be out? It goes into the
50:06 What does a peptide do? Does peptide freak out when it gets into
50:10 water of the blood? No, a peptide. It likes water.
50:15 it hangs out and says, hey at me, I'm just cruising along
50:18 I'm happy and I can do whatever needs to be. Now we can
50:22 what we say is it dissolves easily the extra cellular fluid. It doesn't
50:27 a carrier. Now all molecules have half life. All right. And
50:33 you just don't want things just floating just doing whatever they want to
50:36 And so typically what will happen is there's something you want to preserve for
50:39 longer period of time, you may something come along and bind up to
50:42 to help increase this its half But for the most part these are
50:48 free circulating and you know, they'll find their targets or they won't.
50:53 they have these short half lives in of their action right there, lipa
50:58 or water or sorry, hydra So they have to act through that
51:03 surface or that plasma membrane receptor water soluble equals I can't get into
51:09 cell. Therefore I have to use receptor at the surface of the
51:13 So any cell that I'm gonna come that has my receptor I'm gonna respond
51:17 . But if it doesn't nothing I do about it. All right.
51:22 so we're gonna get that cascade of because it's using those pathways we've already
51:26 at so far. So good. pretty easy. Alright. Oh.
51:31 I would point out, so most these come out, you know,
51:34 start off as these large proteins that have really any function. And then
51:38 you do is while they're in the or even in their vesicles, they
51:42 chopped up and reorganize and you get sorts of fun stuff. And
51:45 these are things you have to memorize . But here's the pre pro
51:49 So you start off as a pre hormone then you get processed, you
51:52 a pro hormone and then you get up again, you become the
51:55 right? So there's levels of So here the pre pro hormone gives
51:59 this which when it's process gives you uh tyra tropic releasing hormone. All
52:07 . And then it gives you a of other things. Here's a fun
52:09 , propio Melanie Kortan. That's a scary name. P. Com.
52:14 . And what does it give you number one hormone number two. And
52:19 number three. So three, for price of one and all you're doing
52:24 you're taking and chopping it up. right, you're looking at that
52:26 I don't know these hormones don't don't me out. Okay. How about
52:30 one? You guys pro insulin you what insulin is. Look, it
52:35 cleaved you get insulin insulin is a and then you get a c peptide
52:41 basically sits and does nothing actually. think I saw a paper a couple
52:44 ago thinking they actually discovered a function that. But we you know
52:50 But the idea is is everything is processed when you're peptide hormone, there's
52:57 processing that takes place inside the cell your release and then when you're released
53:02 you go, buying your receptor signaling occurs activity of the cell changes in
53:07 target cell so far with me. huh. If I talk fast,
53:13 don't just sit there and go, get it later. I mean honestly
53:16 wait a sec I'm not getting You talk too fast, I talk
53:19 fast. No. So so the is gonna be during the making of
53:28 cell. So right up here you see here's my uh pre pro
53:32 there's my pro So there's the first processing. Now I'm going through the
53:35 I'm being reprocessed here it is cleavage the vessel in which I'm actually being
53:41 and then when I'm released now I'm . Alright, really? Your functional
53:46 and when you're released now you can and actually find your target. This
53:50 just an example. All right, anything new on that slide,
54:02 What do you see there? Liggins receptors? Yeah. So how do
54:11 hormones work through all those different weird that we didn't memorize. We just
54:17 they exist out there. So when learn one like let's say and we're
54:23 doing in this class but let's say learning the insulin pathway. You'd learn
54:27 Liggan insulin, you'd learn the Oh where's my insulin receptor? Well
54:32 it is. I need what this right here. I was hoping it
54:38 showed the insulin on there but it's All right, so I got to
54:42 the dime er and then what pathways and then you'd see all the pathway
54:46 . Alright notice it just tells you relation. Okay well what about?
54:53 I don't know. FSH Well I'll using that pathway up there and then
54:59 gonna have to learn all the little along the way you know? But
55:03 do we have to know the nope we just know these are the
55:07 of receptors we're gonna come across then have these god awful things. I
55:14 steroids actually that's what I worked worked with steroids, androgen receptor the
55:18 nine yards and I love throwing this up here because it freaks people
55:23 How much time do I got 25 . All right, I got time
55:27 a story, this is why I myself stuck alright about three years ago
55:34 was a S. J. S. J. W. Is
55:39 justice warrior in the U. She was very upset that men couldn't
55:44 pregnant and so she was like you what this was in the newspaper.
55:49 was in the new york Times or . New york times is like the
55:51 times. She was like you know not fair that women have to suffer
55:55 pregnancy. Men should have to do too. And we should force all
55:58 to take progesterone so that they can pregnancy just like women do. And
56:03 read that I said this stupid idiot never taken a science class in her
56:07 life because she doesn't know how steroids made. If what you're looking at
56:13 in this little picture right here. there's cholesterol. All the steroids of
56:16 body start off as cholesterol, And then given which enzymes are available
56:21 your body, you're going to produce whole bunch of different types of hormones
56:24 different types of steroids. All And so the steroids in this particular
56:30 or the enzymes to make the different are represented by the bars that you're
56:34 here Now this isn't the whole These are the big boys. All
56:38 . These are ones when we think steroids is what we think of.
56:41 up here these are the mineral core down here. The glucocorticoids over there
56:44 the projections over there. The androgens what you'd call the testosterone. And
56:48 over here in the big triangle as estrogens. Now let's take a look
56:51 this and presume of course that men what type of hormone for the most
56:56 testosterone. What do women mostly make progestin? But yes estrogen's alright.
57:01 if I give men a whole bunch progestin, what's going to happen to
57:06 progestin? Here's the progestin and we the enzymes and it's gonna become
57:17 So those stupid men who can't have who don't understand what it's like to
57:22 pregnant, we're gonna give them progestin we're gonna make them more manly.
57:30 this is why we have fun when read the newspaper. Alright again you
57:36 not need to memorize this. But now know where all the steroids come
57:40 . All. Yes sir. So . So barry bonds. Um And
57:50 I'm thinking of Sammy Sosa. Sammy Sosa and a couple of others
57:54 injecting themselves with growth hormones. Which can have an anabolic effect.
58:00 back in the day before we got try to get sneaky and go we're
58:03 use growth hormone. What we're doing we're injecting injecting with androgens. So
58:08 anabolic steroid which anabolic steroid. I remember. I don't think I think
58:12 was five DHT. But I may wrong. It might have been androstenedione
58:17 it may be one and then they it so that they could mask the
58:20 and stuff like that. I mean are literally different methods in which you
58:25 to circumvent the rules of the right? So anyway. Yeah.
58:30 huh. Bring it baby. Alright. You're making me go down
58:48 real big rabbit trail. Usually wait reproduction to get to this um Dhe
58:55 di hydro testosterone right? There is weakest of the androgens women. You
59:00 tons of this stuff. All And it's what causes, I mean
59:04 what used to bring yourself forward into estrogens. You produce those and so
59:09 men men produce those as well in adrenal glands? Alright interesting. And
59:13 own that's another one that's the in is being produced. Not very particularly
59:18 , relatively speaking. Dhe a relative testosterone what we would call testosterone this
59:24 boy right there. It's about um I remember correctly it's about 100 fold
59:30 powerful. Right? So if I'm 100 molecules of D. H.
59:35 . A. That's equivalent to one of testosterone in terms of its activity
59:40 and anabolic effect. DHT is five 2 to 10 times more powerful than
59:48 . So really the major effects testosterone converted into D. H.
59:53 And that's when you get the that's we're big and strong and powerful and
60:01 does that make sense? So in words there is a stepping stone DHT
60:06 the most powerful. It's more powerful testosterone testosterone is way more powerful than
60:11 and I own which is more powerful D. H. E.
60:14 In terms of its anabolic effects. again though if you're looking for someone
60:20 cheating, what are you looking You're looking for the ratios of these
60:24 hormones. And so you what you is you try to circumvent bio.
60:28 me add a little bit of Let me do that. And let's
60:31 what happens and maybe I can mask and yeah. Sorry I went down
60:37 big rabbit trail. All right, , so here we are, 20
60:42 easy. Alright. How do we it? Well, we start off
60:45 cholesterol, cholesterol is brought into the . It's sequestered away because the fat
60:49 carried places you use these different The moment you make the hormone that
60:54 done making in that particular cell out goes you cannot store a lipid soluble
61:00 inside of ethical because it's a lipid layer. It's just gonna go see
61:06 nothing holding it there. So you it as you need it. That's
61:11 one. So to see how different is than the other. Right?
61:14 the signal comes along and says you to make this now. So you
61:17 it. And out it goes all in terms of circulation it is water
61:23 , it is lipid soluble. So it goes out of the blood do
61:26 think that steroid is happy? No like find me someplace safe. So
61:31 have to have a carrier molecule. every one of our steroids has a
61:37 carrier, I shouldn't say everyone, not sure if that's 100% true.
61:40 many of our major steroids have carrier that they use to directly carry those
61:47 through the body. So you have binding protein, you have glucocorticoids binding
61:52 . And that's what moves these steroids the body. There are other non
61:57 carrier molecules like albumin can bind up sequestered away so that you can carry
62:03 hormones through the blood. Now, rules of mass action work on these
62:08 . So again, you're trying to a balance. So there's a portion
62:11 the hormone that's not being carried, a portion that is. And so
62:16 when those molecules become available, if is a cell it can sneak into
62:21 cell and there happens to be a receptor it binds that receptor, it
62:25 on. If it doesn't, it back out and just goes back to
62:28 bloodstream and this stuff has very, low um half lifes. And so
62:32 stuff gets chewed up fairly quickly. you can kind of see how it's
62:36 of moves back and forth. And I'm comparing three versus bound and I
62:41 away a free what happens to You guys you learn this in chemistry
62:47 ? If I have a free molecule bound molecule and take away and the
62:50 is 1 to 1. If I away this what's gonna have to happen
62:54 that bound up molecule has to it to be released, right? And
62:58 says wait a second and again if at 1 to 1 right, you
63:02 have a molecule can't it can't be free and half bound but it can
63:06 half the time free and it can half the time bound. And so
63:11 just follows those simple rules of mass that you guys learned way back in
63:15 . If you ever wonder why we to take chemistry because we have to
63:18 those silly things. All right. how does it work? How do
63:23 steroid hormones work? Well you bind intracellular receptors, Those nuclear receptors.
63:29 bind them. They trans locate the . They hype. They dim arise
63:34 then once they dim arise then you're get a change in transcription. Gene
63:38 . So new genes are being made old genes are being turned off and
63:43 activity of the cell changes the function the change in gene activity. That
63:49 of makes sense. So how many do we have up there? Anyone
63:54 counting while we're flowers rambling. 14, 17 hormones. And there's
64:03 about 20 of them that aren't listed there that are all on there.
64:07 should be part of that kind of groupings. Right? And they all
64:12 that. So peptides. Doesn't matter the peptide is gonna behave one way
64:18 are gonna behave another way. So is just that picture of trying to
64:22 you here is the steroid goes in to its receptor. Oh look here
64:26 dim arised now. I'm gonna get transcription. I get new proteins.
64:29 proteins do new things so that shouldn't foreign to you. All right.
64:36 means All right. We have the are going to be derived from either
64:45 or tryptophan. Tryptophan results in melatonin like melatonin Yeah tyra scene for the
64:54 and you guys know the catacomb means yeah dopamine epinephrine and norepinephrine. So
64:59 know them you just don't know them as a group. There is a
65:03 of the cat. A cola means there so you can see they all
65:05 alike. Here over here is thyroid . So what do we do with
65:09 home? We're gonna learn how to it a little bit later. But
65:11 you take two tire scenes jamming together put a bunch of iodine on
65:15 All right. It's it's more But that will work for today.
65:20 , so the cat a cola means is where it's weird. The cata
65:24 means act like peptide hormones. So bind to what type of receptors?
65:33 surface cell membrane plasma membrane receptors. surface receptors, thyroid hormone acts like
65:41 . So what do they buying nuclear . All right. But once you
65:47 how a uh a steroid respond and a peptide responds and then you just
65:53 these two and throw them in their . You know how all the things
65:57 ? Water soluble itty makes the biggest . Right? Unless you want to
66:03 this as a separate category, you or whatever other category where you want
66:07 do it. So if you understand soluble itty versus water soluble itty,
66:12 you just know which category to put two things you're in good shape.
66:18 ? So this is just showing you cola means what they do,
66:23 So they can be inhibitory it they be stimulatory but they act through those
66:31 . Once again you can use a like this to help you understand,
66:36 not gonna fill it out but you do it at your leisure. So
66:42 is to confuse the people are taking chronology and to confuse you a little
66:45 because that's why all those strange Some rules about some hormones.
66:53 a single hormone or single gland can more than one hormone. Okay,
66:57 not hard. Right, So for the pituitary produces six different types of
67:01 . Alright, that's easy check But a single hormone can actually be
67:06 by more than one endocrine gland right . Alright, so we got things
67:10 some out of statins. Simvastatin is in the hypothalamus Simvastatin is also produced
67:15 the pancreas and depending on where it's secreted and why you kind of get
67:19 results because he has different targets which kind of confusing. Single hormone can
67:25 more than one type of target Alright, fine, insulin can act
67:29 muscles. They can act on you can act on fat in different
67:35 . It cause different responses in the , right? Different targets are going
67:39 get different responses and the rate of can vary over the course of a
67:43 or a course of a month or course of a year. You have
67:47 rhythms for example. And the amount of now I'm blanking because I'm of
67:54 I would um I'll come to an of cortisol had cycle in my
68:00 That's why I'm stuck amount of You have the lowest level cortisol during
68:03 day, you have the highest level in the evening, basically cortisol levels
68:08 with stress. What does that tell day is kind of stressful, but
68:13 basically you responding to your environment. cortisol levels naturally arise over the course
68:17 the day. The menstrual cycle is a clear example of looking at
68:21 hormone start like estrogen starting off low over time it grows and grows and
68:26 , it peaks, it drops and it kind of grows again, kind
68:28 hangs out over here and then it again. So depending on with where
68:32 are in the 28 day pattern, estrogen levels are gonna be different.
68:37 , so pattern of expression changes or different in different types of systems.
68:47 , A single target cell may be by more than one hormone.
68:51 what we're doing now is we're dealing gas and brake pedals. Have you
68:54 pressed on the gas and brake at same time that first day you're
68:58 Maybe? Yeah. Yeah, I a couple heads going up. My
69:02 did that the other day. It like, please don't. Yeah.
69:06 right, so one is a gas , tells the cell to do one
69:09 . The brake tells the cell to the opposite thing. And so what
69:12 doing is you're regulating the cell between two different hormones. All right.
69:17 all hormones do that. These are examples. It's an anglican, progesterone
69:20 acting on their cell types. These just examples. You don't need to
69:24 them. A chemical messenger. Can a hormone. Alright, that's
69:29 It can be a neurotransmitter what depending upon where it's released and
69:35 So, for example norepinephrine, when secreted by the adrenal medulla, it's
69:41 in the bloodstream. So we call a hormone, but when it is
69:44 by a sympathetic ganglion fibers, we it a neurotransmitter. So it kind
69:50 describes its behavior. That's why that gets kind of fuzzy, so it's
69:55 descriptive of activity and then this is kind of fun organs are either exclusively
70:02 in nature, like your pituitary gland it can perform non endocrine functions.
70:07 have to test this up here. that's not as fun. Let's use
70:10 stomach. When you think of the . Do you think of an endocrine
70:15 ? No, but it is it tons and tons of different hormones.
70:19 when you think of the stomach, do you think of digestion?
70:24 So that's an example of an organ has multi function. Or if you
70:29 to stick with the testes, that's too. In terms of hormones,
70:33 are can be permissive. And so here is just an example of
70:37 Here, you can see thyroid It doesn't have any effect on reproductive
70:42 . If you give steroids FSH and two a mouse, it doesn't really
70:47 a major effect on reproductive development. basically kind of pushes you along but
70:51 really do anything. But you put of this together. Thyroid hormone makes
70:56 permissive or permissive towards reproductive development. ? So, it's not just these
71:03 things. You need to have that order for these things to work.
71:06 gives it permission for their activity. what we mean by permissive synergism has
71:11 do with biology. Math. And a special term that I've come up
71:15 . All right. So one plus equals no. In biology it's
71:20 Mhm. Right. See look here's and epinephrine right there. All kind
71:26 low you put them together. That's the some of those are of these
71:30 and that up there? When you them all three together, it's like
71:34 . That's a one plus one plus equals 300 Right? Or 111.
71:41 it's it's not just additive, it's in terms of its activity. So
71:46 you hear synergistic what it means is these two things come together you get
71:50 much larger response than each of the parts added together. Alright, so
71:57 plus this isn't gonna give you a but these two added together is gonna
72:01 you something much much bigger. Lastly here's where the hormones basically battle against
72:07 other and I love using progesterone and together. Progesterone. So imagine pregnancy
72:13 we're we're late. Third term progesterone says no no no no contractions.
72:18 time to give birth, estrogen on other hand says time to give birth
72:23 time and one is telling the other down regulate the receptors of the other
72:28 . So they're basically battling each other determine which one is going to result
72:33 labor contractions. And so very late pregnancy estrogen takes over and drops the
72:39 of progesterone receptors. So progesterone no has anything to buy into their go
72:43 you start getting increased contractions. It's the only way that works but that's
72:47 of it. Yeah. Why does happen? So the idea is each
72:55 is basically trying to promote a specific and so rather than trying to create
73:00 system that is that can be What you just want to have is
73:04 want something that's just going full blown you just want to cut it
73:07 In other words, it's it's it's trying to regulate here and down here
73:11 down here, it's just sits is , we're gonna make this happen,
73:14 we're not gonna let you do anything it. Why pregnancy? Well,
73:22 it's a little bit more complicated. mean, whenever I'm doing stuff like
73:25 , it's always more complicated. There two different types of progesterone receptors.
73:28 two different types of androgen or estrogen . There's alpha beta and really what
73:32 doing is you're swapping between which one being expressed at which time and so
73:37 regulating. So you imagine during do you guys want to go through
73:41 during pregnancy? No, because you , you're you're well, you're you're
73:47 the middle of it, right? you want to wait for that,
73:50 fetus to come to term. You it to be ready to. I'm
73:54 say it this way, even though not true, live on its own
73:57 babies don't live on their own. are literally going to be attached to
74:01 for like three years. All But you want that thing to come
74:05 term, you don't want it to growing before it's ready. And so
74:09 idea here is progesterone is promoting that saying, hey hey, you
74:13 we want to make sure this goes turn, but estrogen is being expressed
74:17 a way to begin ramping up towards contraction. And so the idea is
74:23 you have the battling taking place where one is being suppressed, but the
74:27 one is promoting, but as this begins to, the expression begins to
74:31 and stuff like this, this one take over now. So in other
74:35 , it's not a binary, on , it's a slope as one goes
74:38 and one comes down, it's kind a better way to kind of look
74:41 that. Yeah, no, it be true, it's not always
74:50 but very often you'll see it's oh this doesn't work by itself.
74:54 a lot of claims we make about and then we find out that
74:57 no, it's part of a large system, like when we say growth
75:01 dependent upon growth, it's not it's a regulator of a whole bunch of
75:04 molecules that are responsible for growth Time, five minutes. Alright,
75:10 we may not get through them but we're getting close. Alright,
75:13 I want to show you here is structure of the pituitary gland.
75:18 And so here what we have is have two parts to it. We
75:20 the anterior and the posterior pituitary in particular image, you can look up
75:24 and see which way am I pointing side over here is the front.
75:27 is the back that's anterior. That's here. If you can't remember your
75:30 area, just think about where mommy to do. That's your posterior posterior
75:36 ? So posterior is a neural The anterior is glandular, it is
75:44 neural but it's neuro glandular and neuro . Alright, so those but it's
75:50 type of structure, the type of type of neuro glandular same thing.
75:57 are neurons. These are not. an epithelium. Alright. So the
76:03 released from the pituitary are controlled by structure up here. The hypothalamus.
76:08 interior is regulated through hormones that are from the hypothalamus into a bloodstream through
76:14 portal system that then acts over here the anterior the cells in the anterior
76:20 . When you're dealing with the posterior cell bodies of the neurons are located
76:26 the hypothalamus. Those hormones are transported the neuron and the terminal ends of
76:32 neurons are found in the post And so when you get a signal
76:34 release you release it directly from the airier. So really the post here
76:39 just kind of an extension of the . Alright, so the portal system
76:45 refers to the capillary bed, the capillary bed between those two and the
76:49 that we have this is that it's advantageous to be able to tell uh
76:54 send the signal directly to via the to the pituitary gland without it going
76:59 the full body in the full You know how much blood you guys
77:03 in your bodies? About six I heard six liters. I'll go
77:07 liters today, 5.5 4.5 for I mean we can we can you
77:11 , depending on your size, there's sort of put 4 to 6 and
77:15 talking Pekka moller. So if you're with and you put it into six
77:19 of blood, it disappears really But if you can keep it in
77:23 very very small circulation then it can a very very powerful effect. So
77:28 taken directly to its target. Um so I've already just kind of
77:33 this, this is basically the same , the two hormones of interest.
77:37 and oxytocin. vasopressin. Oxytocin are closely related other species, other
77:43 other birds stuff. They will only one. So they are very closely
77:48 . Um vasopressin plays a role in water levels and water solute distribution.
77:54 basically water salt balance oxytocin plays a in regulating contraction. Also interestingly in
78:01 . It plays a role in um not gonna say physical attraction but bonding
78:06 probably the better thing it's used when giving birth. Oxytocin is there that
78:11 you bond with your baby, And also if you can imagine during
78:15 , oxytocin release, it creates bonding in men after intercourse because you really
78:20 release oxytocin as well, it makes fall asleep. Now. If you
78:26 about that, you can see now guys are like you know sex I
78:30 I want out of here, That's kind of the male behavior.
78:33 you've watched enough sitcoms and says like we're done um men fall asleep,
78:39 cuddle and all of a sudden everyone's , right? And that's where we
78:43 that bonding through that particular hormone. the love hormone. Alright.
78:49 So the cells that are found up that produced the a th or
78:54 they're they're they're intermixed. They're found two different regions um which you don't
78:58 to memorize. But when you look a cell that cell is either going
79:01 produce vasopressin or that cell is gonna oxytocin, they don't produce both.
79:05 you get one or the other, don't get both from the same
79:10 And I think what we have managed keeps going, doesn't it? 11
79:15 . Okay, so with the anticipatory are the hormones you need to
79:19 All right, we have these hormones primarily responsible for regulating um the release
79:26 of downstream hormones. In other words they're releasing hormones, they're regulating
79:31 Alright. So we have um with exception of oh yeah prolactin is the
79:38 that isn't. Alright. But what was looking at but here everyone has
79:41 regulated by a single hormone up in hypothalamus. And then when you get
79:45 into the pituitary and you're dealing with . Growth hormone they have releasing and
79:50 inhibiting hormone and then all these these the tropic hormones. That's what we
79:54 to these pituitary hormones as tropic or . That just means they regulate other
79:59 . So prolactin controls milk, contract milk production, not contraction which is
80:05 . Oxytocin FSH and LH DSR collectively gonadotropin. They regulate the hormones of
80:10 gonads, thyroid stimulating hormone stimulates the adrenal, cortical tropic hormone, adrenal
80:20 . Yeah. And then finally growth is a somatic stat and it regulates
80:25 etcetera etcetera. And that's just the . Oh I got feedback loops which
80:29 get to later. Ah Yeah so question is do we need to know
80:35 hormones start learning those hormones? Oh tiring? Yeah. For the anterior
80:47 . Those are you need to know to enjoy your weekend. No I
80:55 go back to my office and then going home. I gotta get that
80:59 sock off my
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