Endocrinology | Receptor Pathways

all engine n what we're going to do in this video is we're going to talk about the various different types of receptor Pathways now to go over every single type of receptor for every single hormone it's just it's impossible to do all of that in this video so what we're going to do is we're going to focus on the most important receptor Pathways okay now before I do that let me explain something because we can't just Dive Right into these Pathways and not explain why we're doing them so hormones there's two different types of hormones

right so we can really Define hormones two different ways we can say some are actually going to be peptide hormones right or some are actually going to be steroid hormones now why am I telling you that because peptide hormones are what we refer to as water soluble meaning that if you put these proteins into water it'll actually be able to have its hydrophilic amino acids interact with the water it'll be soluble in the water all right it won't precipitate okay so in other words we can say that peptide hormones are what's called water soluble but

here's the problem if you look at an actual cell so let's say I draw a cell here let's say here's just a general cell right so look at this guy he's he's ready to be stimulated now here's the problem let's say I draw here in blue a peptide hormone now a peptide hormone the problem with peptide hor hormones is that they can have charges and they're pretty big too so they can't just fit through this cell membrane why one reason is because it's too big the second reason is because the membrane is actually made up

of phospholipid bilayer so if it's lipid Sol if this if this actual membrane is a phospholipid Bayer a protein can't move through it right so it's because it's not going to be soluble within the lipids it's water soluble so in other words this protein can't penetrate through this cell so the only way that this protein this hormone can exert its effects on the cell is it has to do it on a certain type of receptor there has to be a receptor on the membrane that this hormone can bind onto and then in this a cell

there's actually going to be these Messengers that can send signals all throughout the cell to perform the action of this hormone now these messages that are occurring inside of the cell from an extracellular membrane receptor is going to be through what's called second messenger systems so these peptide hormones are going to work through what's called the second messenger systems right we're only going to focus on two significant ones okay one we're going to talk about the GQ pathway and one we'll talk about the G stimulatory pathway okay and we might even discuss a little bit

about the G inhibitory pathway but in other words we're talking about the second messenger systems and how these hormones are working on these receptors and in U mediating these intracellular responses okay now with steroid hormones they're a little bit different steroid hormones are lipid soluble and the reason why is they're derived from cholesterol okay so because they're derived from cholesterol they're lipid soluble meaning that they don't have to have a receptor on the outside of the cell they can have receptors present inside the cell why because let's say that this is your lipid hormone right

here if he's a lipid hormone or a steroid-based hormone he's lipid soluble right he can pass right through the lipid B layer and come and bind onto a receptor inside the cell so we're going to focus on just a generic pathway for steroid hormones and how they exert their effects now now that we've done that let's go ahead and just list a couple peptide hormones and a couple steroid hormones that way we know and I'm just giving you a couple we could say here for peptide hormones I could be mentioning FSH I could mention LH

I could mention growth hormone I could mention glucagon I could mention parathyroid hormone and insulin and the list could go on and on and on oxytocin ADH but the basic idea is to know that these peptide hormones are going to be working through the second messenger systems and I'll explain what I mean by that whereas steroid hormones we're going to take for example the classics testosterone uh estrogen progesterone aldosterone cortisol gonat corticoids and so on and so forth okay Gat corticoids we could keep listing these we could even say vitamin D and we could even

say thyroxine acts like a steroid hormone but you get the basic Point these guys have to have receptors inside the cell these guys have to have receptors on the cell membrane so now that we know that let's go ahead and dig in here so what I did is I kind of blew out a really big cell and what we're going to do is we're going to take it the look at two of these receptor Pathways right here okay so let's go ahead and do that let's say we focus first on this red receptor now these

red receptors that I'm drawing drawing here it's actually coupled with what's called a g protein so inside of the cell I have what's called a g protein so these are called G protein coupled receptors okay so this is called a gr protein coupled receptor now a little bit about their structure protein wise if you notice I drew a line here it's passing through the membrane seven times watch 1 2 3 4 five 6 7even so they call these seven pass receptors seven past trans transmembrane receptors or Serpentine receptors now let's say for this specific G

protein this specific one we're going to take a look at what's called G stimulatory so G stimulatory protein so here's our G stimulatory protein so now what's going to activate this G stimulatory protein so let's say I have a hormone here a peptide hormone let's say for example I just pick by random epinephrine okay here's my epinephrine and epinephrine binds onto this receptor when he binds onto this receptor what it does is it changes the overall three-dimensional structure of the inside portion of the receptor and activates this G stimulatory protein what's this G stimulatory protein

normally bound to okay normally this G stimulatory protein is bound to what's called GDP so normally it's bound to what's called G DP but when epinephrine acts on this receptor and changes the overall threedimensional structure this receptor activates this G stimulatory protein and it displaces the GDP and adds on GTP so now look what we're binding on we're binding on to this GTP and what do we do we get rid of the G DP okay so now GDP is actually going to be gone so let's show that here so look now look what it looks

like after this so This G stimulatory protein actually can move it's a peripheral membrane protein right so now look at it here he is right here G stimulatory protein he's activated why is he activated because he's bound to GTP so we can show here bound to him is GTP he's bound to him okay he's activating this guy now what does this G stimulatory protein do he goes to this affector enzyme that's present on the cell membrane okay so let's draw here an affector enzyme so let's draw this nice little affector enzyme this guy has a

specific point of an attachment for that g stimulatory protein so G stimulatory protein is going to come in and it's going to perfectly attach to this enzyme right here so look it comes in and it attaches to this enzyme when it attaches to this enzyme this enzyme becomes very very active so let's show the GTP here GTP is still bound to the G stimulatory protein this enzyme becomes Super Active what's this enzyme here called this enzyme is called a denate cyclas what a denate cyclas does is it has a specific enzyme look at this it

has an enzyme and this enzyme has like a cutting portion here look at this he's got the teeth right there like look his legs have teeth so his legs have teeth so what's going to happen this enzyme right here is actually going to cut the GTP so what is this enzyme here called it's called a GTP Ace so when it cuts the GTP what does it do it converts GTP into GDP what was GDP doing to the G protein it was keeping it off it was the off switch what was GTP doing to this it

was the on switch it was turning this guy on well before it was on now what when the this GTP cuts that phosphate so what is he ripping out of there he's ripping out of this a phosphate he turns off this G stimulatory protein because now now this is no longer GTP bound it's actually GDP look at that now what happens from him cutting that GTP into GDP he then uses that energy to convert a very important molecule which we know ATP he converts that into cyclic okay so then he converts it into cyclic then

cyclic guess what he does does he comes and he activates a very specific enzyme so let's say that this is this enzyme right here and we're going to draw this one in green this enzyme is actually going to be a protein kinase so here's our protein kinase what is cyclic do cylic comes over and activates this protein chasis it doesn't have to just be one it can activate multiple protein kinases and then guess what these protein kinases are going to go and do this is where it can go and do a ton of different thing

now here here's what you need to remember what a what's the definition of a kinas a kinas by definition is something that phosphor relates right so it's a good phosphorilation so phosphorilation of proteins and enzymes and different types of substances right so what is this protein kyia going to do he's going to go and phosphorate tons of different proteins and enzymes so let's show that here so in cyclic acts on him he becomes active because previously he was inactive but when cyclic on him he becomes very active and look what he can go and do

he can go and do what's called phosphorilation of various proteins proteins right so if phosphor various different types of proteins what can those proteins do it depends on what the protein is for example let's say that one of the proteins is embedded here on the membrane let's say this is this this protein right here and this protein will only open this channel let's say it's a channel protein and this channel protein is normally closed in the cell but then this protein kisee a he comes over here and he puts a phosphate group onto that protein

and then the protein Channel opens and then certain types of ions can flow in for example maybe it could be for calcium maybe it could be for sodium whoever knows but it could be causing ions to flow in or flow out so it doesn't just have to be for ions coming in it could be for ions to go out it just all depends on on the the cell right generally you're going to be having cat I coming into the cell but in general just know that this phosphorilation could do what it could change the membrane

permeability of certain ions you know it could also activate a different a lot of different enzymes let's say that you're trying to do glycolysis in the cell so you're trying to convert glucose into pyruvate well you know there's a lot of different enzymes that regulate these metabolic pathways guess what this guess what this protein can do he can come over and he can put a phosphate on these enzymes so he can regulate metabolic pathways he can regulate the membrane permeability tons of different things guess what else he could do you know there's also proteins over

here that really really are important for being able to control transcription and and a lot of different other properties guess what this guy can do he can come over here and he can do phosphorilation of this this transcription Factor let's call this a transcription Factor TF and guess what that could do that could come into this actual cell activate these genes and make new proteins so it can actually cause new proteins who knows it might even cause the cell to proliferate too so it could even cause cell growth so it can cause cell growth tons

of different effects so if you see here this one hormone can act on this cell and produce a plethora of effects it just depends on what the cell's function is I just want you to get the basic idea here that what can protein kyes do he can phosphorate various different types of proteins what are those proteins it depends if it's metabolic it can maybe regulate certain types of enzymes and glycolysis or gluconeogenesis or glycogen metabolism who knows it could phosphorate proteins for membrane channels to change the ion permeability it could phosphorate different types of proteins

that control transcription or different types of proteins that control DNA replication and cell growth so a lot of different effects that can come just from this one single pathway all right now that we know that this next pathway is going to be even easier okay so let's go ahead and zoom in on this pathway now but now I'm actually going to draw him over here I'm actually going to redraw him over here so we don't run out of room so let's actually draw him right here now the difference between this protein and the one that

we just did is depending upon the G protein so it just really depends upon the actual G protein so we mentioned G stimulatory protein I'm going to mention another different type of protein this protein is actually going to be called GQ okay this is called GQ protein now there's certain types of hormones that can activate this pathway and I'll explain which hormones for right now just let's go with um oxytocin so let's say for this one we say oxy tocin okay so oxytocin comes in and binds onto this receptor when he binds onto this receptor

he activates this GQ protein what was the GQ protein bound to originally it was originally bound to GDP but when this oxytocin binds onto the receptor it changes its shape and activates the GQ protein so what does it do it actually binds on GTP and gets rid of the GDP all right now it's active right so it's active what is this GQ protein going to do well you know there's enzymes again on this actual cell membrane what is this enzyme that we could have here let's draw this enzyme right here look at this guy so

this guy is kind of like a blockhead right look at this all right and what's he going to do he's actually going to have a specific domain over here that when this GQ protein binds on so let's show the GQ protein coming over and binding on perfectly to this point right here so there the GQ protein binds and the GQ protein is bound to GTP right same thing going to happen but this enzyme right here is very very specific this enzyme is called phospho lipase c what does phospho lipase C do well he does the

same thing that the adental cycl does so he has a little ear over here look at his ear his ear it's a heck of an ear right it has this little cutting domain and what it does it actually cuts the GTP P what does it cut it cuts the third phosphate out and converts GTP into GDP what does GDP do to the G protein it turns it off while GTP turns it on so now this g protein's off then what happens is phosph Lipa c will cut a specific molecule in the membrane this specific molecule

that it cuts in the membrane is actually called p i p two which stands for phospho in ayal diphosphate what does this guy do now look at the other part of them so now he's got this actual he look at his chin his chin has got this little part right here that it loves to cut look it's going to cut this actual pip2 so what does this guy do he has this part here that cuts the pip2 and it breaks it into two different fragments what are those two fragments all right one fragment that it

breaks into is called specifically it's going to break down into d a which stands for D AAL glycerol and the other component of it is actually going to be I P3 which stands for anal triphosphate now D which is the dial glycerol he can go and activate a specific enzyme that specific enzyme that he can activate is actually called protein KY C okay so he can go and he can activate a specific enzyme let's say that specific enzyme is called protein kise C so now look it activates this protein kise C and what can this

protein KY C do just what the protein kyes a could do so what let's just actually write that out what could he do he could do phosphorilation of various proteins and then what's the overall result it all depends phosphorilation of proteins we said can either uh change the membrane permeability it could change the it could actually control metabolic pathways it can control the protein synthesis it can control cell proliferation you know sometimes phosphor a protein can even inactivate the protein too so phosphorilation doesn't always activate something it can also deactivate something okay so that's the

point there what does ip3 do okay you know most cells have what's called a smooth endoplasmic reticulum so let's say I draw here a smooth endoplasmic reticulum so here's our smooth endoplasmic reticulum on the smooth endoplasmic reticulum or even in certain cells like muscle cells they have what's called a sarcoplasmic reticulum so this could be a smooth e so I'm going to put here it could be smooth ER or it could be a Saro plasmic reticulum it just depends on the cell so it could be one or the other so if it's in like a

general cell that's not a muscle cell it be a smooth R if it's in some type of muscle cell it could be a SM sarcoplasmic articul right like cardiac muscle or like the actual skeletal muscle and a little bit in smooth muscle but anyway what's the point here on this smoothie r or this sarcoplasmic reticulum they have these specific receptors for ip3 so let's draw the specific receptor so here's the specific specific protein and on this protein it has a very specific receptor let's say let's say this in blue here's this receptor and that's for

ip3 ip3 comes in and binds onto this receptor when he binds onto this receptor it opens up a specific Channel and guess who starts flooding out into this area calcium so calcium is going to start getting pushed out into the cytoplasm what's the significance of calcium calcium loves to bind onto calmodulin and guess what calmodulin helps to do it helps helps to activate specific types of kinases and those kinases can perform various different types of functions okay some of them could be kinases could phosphorate different types of proteins to initiate contraction if it's a muscle

cell and that's why I wanted to mention so let me actually mention this right here so again calcium can actually come in let's actually show it over here can Bine onto what's called calmodulin and when it binds onto calmodulin it can activate other different types of kinases so when this actually can come and activate other different types of kinases and then again what can kinases do we can just draw this going in right here look it can phosphorate various different types of proteins right and what can that do in this case here's what I wanted

to mention why I mentioned oxytocin so oxytocin is a very specific one because we know oxytocin is important for being able to regulate contractions right of the actual uterus or of the myoepithelial cells and the milk ejection or the vast deference all that stuff how remember I told you it was designed to increase calcium inside of the cells this is the mechanism that it works through so oxytocin can actually activate this Pathway to increase the calcium levels in the cell why because calcium can either bind onto troponin or it could activate calmodulin and those could

activate kinases they could phosphorate different types of proteins like mein and then do what trigger muscular contraction but that's obviously not the only thing that could happen with this pathway it could also phosphorate various different types of proteins that could control membrane permeability cell proliferation right so it can still do all of these different things that he showed up there it can control metabolism it can control cell proliferation protein synthesis various different types of Pathways okay that covers that one now we're going to finish up with one more okay one more pathway here let's actually

show him over here on this side all right so let's show this guy in red let's actually show him inside of the nucleus okay so this is actually going to be for the steroid hormones now okay now there's a receptor right there it's an intranuclear receptor now I told you steroid hormones have receptors either inside of the cell right and that inside of the cell means it could be intracytosolic or it could be intranuclear it honestly depends upon the steroid hormone okay so usually these guys when they're not bound to steroid hormones they're bound to

something which is referred to as HSP which stands for heat shock proteins now a steroid hormone what do we say it can diffuse right through the lipid Bayer so let's show that in blue here so say here is my steroid hormone and I take for example this steroid hormone this could be testosterone okay but it could have been any of them I'm just picking this one as an example and what does it do it actually moves right through the membrane so we can show it actually diffusing through the membrane then what does it do it

actually can actually move either if it's in the cytool it can bind onto that receptor displacing the heatshock proteins or if it's in the nucleus it actually will move right into the nucleus and look when it binds on to this actual intra cellular receptor receptor it displaces the heat shock proteins now the heat shock proteins are displaced this receptor that it binds on to is now very active and look what it can do it can bind on to a specific Gene sequence what is that Gene sequence that it binds on to let's say I highlight

this portion that it's B binding on to I'm highlighting this this right here this specific Gene sequence is called a h r e you know what that stands for that stands for hormone response element so it's a specific Gene sequence that whenever these actual hormone receptor complexes bind onto that Gene what could it do it could trigger a a plethora of effects it could cause the cell to start proliferating so it can stimulate mitosis it could stimulate the synthesis of more proteins and what could those proteins do they could do various different things they could

control metabolism they can control ion permeability they can control protein synthesis they might be structural proteins they could be functional proteins it can control cell growth we don't know right it just depends upon the hormone okay so again understanding this is critical that testosterone can actually do what move right through the cell membrane it can bind onto an intracellular receptor whether it's in the cytosol or in the nucleus that receptor is normally bound to heat shock proteins but when testosterone binds it displaces the heat shock proteins and when it does it can actually activate what's

called a zinc finger but we're not going to talk about that and that can bind on to the specific specific Gene right which is called a hormone response element and what will that do that can actually undergo what it can undergo mitosis so you could actually cause DNA replication or it could stimulate transl transcription and then translation to make different types of proteins okay last thing I want to mention here is we mentioned how we stimulate all these Pathways well how do we inhibit it because we can't have these things you know we had this

GQ protein coming over here and binding onto this guy and then this whole pathway was occurring how do we actually inhibit this process from continuing to occur because this cyclicamp is rising in the cell right so this cyclic is rising in the cell how do we prevent that cyclic from continuously rising and rising and Rising okay you can use and you can also do this for this phospho Lipa C you can use an enzyme and this enzyme is called so look at this I'm going to show this enzyme like this here here's this enzyme and

this enzyme loves to be able to eat the cyclicamp whenever it's time what is this enzyme called this enzyme is called pde pde stands for phosphodiesterase so phosphodiesterase loves to be able to break down and degrade the cyclicamp why because if cyclic levels increase so much it's just going to continue to keep stimulating the cell so to inhibit it we have to have these phosphodiesterases which will start breaking down this cyclicamp all right and this can also do that to these phospholipase uh phospholipase enzyme also so you can also have that enzyme over there that

phosphodiesterase molecule so look here he is this is also called phosphodiesterase and this could also occur in multiple different types of Pathways but just understanding that these enzymes are the ones that are breaking up the cyclicamp or they could be breaking up the phosph Lipa C or other different types of enzymes to prevent these Pathways from continuously occurring right all right guys I hope this made sense in this video we covered the G stimulatory proteins we covered the GQ proteins we covered the testosterone pathway we discovered why certain types of peptoid hormones have to work

on extracellular membrane receptors and we discussed why serid hormones can actually have intracellular receptors obviously we didn't cover all the different types of receptor Pathways in this video video I hope it made sense thank you guys Ninja nerds until next time