Term
| Types of glands/hormone-secreting cells |
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Definition
• Exocrine: secrete into spaces (external world, GI lumen) via ducts
• Act locally
• Endocrine: secrete into bloodstream (not always general circulation) via capillaries
• Act globally
• Master regulator is the hypothalamic-pituitary system
• Neuroendocrine: neurons that release hormones that act via a blood supply |
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Term
| Other secretory mechanisms |
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Definition
• Paracrines
• Released into blood or interstitial fluid but act locally, including neurocrines
• Autocrines
• Released into interstitial fluid and act on the releasing cell |
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Term
| Types of secreted products |
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Definition
• Simple solutions: hydrochloric acid, bicarbonate
• Complex solutions: saliva, tears, sweat, milk, semen, bile (contain other products such as enzymes, lipids, Igs)
• Enzymes: exocrine secretions of the GI tract, particularly the stomach, duodenum, and pancreas
• Hormones |
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Term
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Definition
This is an example of a duct in the stomach. The stomach ducts have many exocrine cells because a lot of the secretions in the stomach are exocrine. So for example, secretion of hydrochloric acid, of pepsin, of some of the enzymes that are involved in protecting the stomach and digesting the food are exocrine.
That is, the cells that are lining the duct-- so let me get you oriented. Here's the gastric lumen. This is the inside of the stomach, this space. And these cells that are lining the duct that's coming off of the gastric lumen are going to be creating that products into the duct where they will then travel up into the gastric lumen. So HCl, for example, would be secreted in this way.
Some cells-- and they're actually not shown here. But I wanted to show you this because it's a example where you have both exocrine and endocrine. There are some cells usually down in the lower parts of the duct.
There's one particular type of a cell called a G cell. And that releases gastrin, which is a hormone that's released into-- I'm just going to draw a little capillary here. So it'd be a capillary.
And so this G cells of the stomach release gastrin, the hormone, into the capillaries nearby where the gastrin is moved into the general circulation. So it's just an example of a duct that has both exocrine and endocrine cells. Mostly exocrine, but there are endocrine cells in the stomach as well.
So again, we've already seen a little bit of this. But here we have endocrine cells. Endocrine cells secrete hormones into the bloodstream.
It is not always the general circulation. But it's usually the general circulation. And we'll see the examples where it's not when we talk about the hypothalamus and pituitary. |
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Term
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Definition
| secrete into bloodstream (not always general circulation) via capillaries |
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Term
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Definition
| released interstitial fluid but act locally on other cells |
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Term
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Definition
| released into interstitial fluid and act on the releasing cell |
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Term
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Definition
But endocrine cells secrete something into the bloodstream. And here we can see it here by secreting hormones into a capillary. Those hormones travel somewhere and act on a target cell that is somewhere else, somewhere potentially very far away from the cell that released the hormone.
And we talked earlier about autocrine and paracrine signaling. And here's just some images to give you a better example. So again with paracrine signaling, we have a secretory cell that's secreting something into, for example, the interstitial space or even into the gastric lumen, but usually into the interstitial space where that hormone will act on some nearby target cell.
And sometimes the target cell is the cell that actually released the hormone. And that would be an autocrine signaling mechanism. So these are our different types of hormones signaling mechanisms. |
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Term
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Definition
either full proteins or small peptide products of proteolytic cleavage
• Synthesized as proteins • HGH acts as a full-length protein
• Synthesized as preprohormones and cleaved to generate prohormones and then active peptide hormones • Numerous examples: insulin, ACTH, and others |
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Term
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Definition
small molecules derived from amino acids
• Tyrosine derivatives • Dopamine, epinephrine, norepinephrine
• Histidine derivative • Histamine |
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Term
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Definition
| lipid-soluble, hydrophobic, cholesterol derivatives |
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Term
| Types of hormone receptors |
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Definition
• Cell-surface receptors: transduce signals inside cells via second messengers
• Steroid hormones: require carriers, receptors are intracellular, DNA-binding proteins that transport hormones from the plasma membrane to the nucleus and modify gene expression |
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Term
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Definition
So let's look at a couple of examples of second messengers that are activated by peptide and amine hormone receptors. Again, these are typical membrane-bound receptors. We can see one here, the G protein, often G protein-coupled receptors.
The so-called first messenger, which is the hormone itself, is extracellular. It's in the blood if it's an endocrine hormone. And it is going to bind to its site on its receptor on some sensitive cell. This is going to activate a G protein to interact with adenylyl cyclase, creating cyclic AMP, which is going to then go in and activate something like protein kinase A. Or we might have-- that's a very classical pathway, the so-called Cyclic AMP Pathway, which can activate things like calcium release in the cell, which can then, of course, activate all kinds of activity that cells need to do.
Another example would be a G protein-coupled receptor that's linked by a G protein to phospholipase C, which then creates IP3, the second messenger IP3, which can also interact with calcium channels and cause calcium release in cells. So these are very standard second messenger systems used by many of the peptide and amine hormones to carry out their activities. In some cases, some hormones will bind to protein kinases, not G protein-coupled receptors, but actual receptor kinases, which can directly phosphorylate substrates and initiate activity of various signaling pathways. |
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Term
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Definition
And as I said before, the steroid hormone receptor is different now than the peptide and amine hormone receptor. And this is due to the nature of this steroid hormone, which is hydrophobic and lipophilic. So this sort of classical model of how the steroid hormones blind to their receptors is that the hormone, which is shown in blue here, is being carried through the blood by some kind of carrier protein.
Obviously, as with any receptor ligand binding interaction, there's an on- and off-rate. It comes off in the vicinity of a cell membrane. And it vastly prefers the cell membrane environment. It's very lipophilic, so they diffuse into this cell membrane, where they get picked up by the yellow box here, which is the steroid hormone receptor.
The steroid hormone receptor is inactive until it's bound to one of its hormone ligands. And that moves the whole hormone receptor complex into the nucleus where gene expression is altered in response to the hormone. Other ways that this can happen, so other types of receptor interactions, as we saw that the amines and the peptide hormones can activate second messengers. Some of the ways that they interact with their receptors include receptor-mediated endocytosis.
And this can also work for a steroid hormone. Where you have a steroid hormone bound to a carrier, it gets picked up by a receptor on the surface, endocytosed into a lysosomal compartment. And then the lysosomal compartment causes release of the hormone.
And sometimes steroid hormones can also interact through cell surface receptors by interacting with the receptor's interaction with the cell membrane. Because again, these steroid hormones are very interested in that lipid environment of a cell membrane. So once they get into the cell membrane, they can start interacting with the hydrophobic regions of other receptors and all through their activity.
But the classical steroid hormone receptor interaction is this one shown in panel A, where a steroid hormone binds to a receptor that's cytoplasmic. That activates that receptor. It takes it to the nucleus. And you get changes in gene expression. |
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Term
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Definition
-This happens with hormones and other secreted products
Finally something else to think about, when you're thinking about hormone systems and endocrine systems are the positive and negative feedback regulatory mechanisms, which we'll be seeing a little bit more. But this is sort of a general overview in the endocrine system.
So a negative feedback system in the endocrine system would be something like this. The hypothalamus is going to initiate a release pathway by stimulating the anterior pituitary gland to release some hormone that acts on an endocrine gland. So the pituitary hormone will tell the endocrine gland to release its hormone, which it does. Its hormone goes into the blood. That blood can go back to the hypothalamus. And as the levels of this hormone rise, the levels of the hypothalamic-releasing factor that initiated its release start to go down.
Alternatively, it can go to the anterior pituitary. And it can start to reduce the levels of the pituitary hormone that told the endocrine gland what to do. And we'll see a little bit more about this hierarchical structure in another video.
Alternatively, it can go to the anterior pituitary. And it can start to reduce the levels of the pituitary hormone that told the endocrine gland what to do. And we'll see a little bit more about this hierarchical structure in another video.
But this is just so you can see that as hormones are released by peripheral glands, such as the adrenal gland or the thyroid gland, they go into the blood, and they feed back on the master regulatory glands that initially started their release. So that's a negative feedback system when a hormone that's released by some peripheral gland gets into the blood and goes to the brain, hypothalamus, or the pituitary and reduces the release of the hormones that initially caused the glandular hormone to be released. That's a negative feedback.
There are examples, but not very many, of positive feedback where the release of a hormone in a peripheral gland actually stimulates further release of the regulatory hormone so that you get an increase of the hormone. As levels are going up, you get more of that hormone being released. And this is something-- you don't see it very often. But it is seen during parturition and the hormones that regulate uterine contractions. |
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Term
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Definition
So in preparation for considering the endocrine system, I thought it would be useful to do a little video looking at some of the hormones of the endocrine system and how they're synthesized.
This is from your Costanzo physiology book. And it shows the hormones and the glands that they come from. This is a cartoon schematic of the endocrine system. I think it's a good way to start by starting at the top, which is the hypothalamus, and then sort of working our way down, and looking at the different hormones that are secreted by different glands.
So the hypothalamus is the beginning of the endocrine system. And what we see is that the hypothalamus makes a lot of hormones that have an RH ending, TRH, CRH, GNRH, GHRC, and then a couple of other things, somatostatin and dopamine.
So what is this RH? RH equals Releasing Hormone. So the hypothalamus secretes a lot of releasing hormones. These releasing hormones are secreted into small capillaries that go directly to the anterior pituitary. And the anterior pituitary releases a bunch of hormones that have an SH ending. And then a couple of other ones as well.
So what is SH? So SH equals Stimulating Hormone.
I think it's useful to take a moment and talk about releasing and stimulating hormones, because if you can understand what they're doing, you basically have the hierarchy of the endocrine system down.
So the hypothalamus, for example, releases TRH. So what is TRH? That's Thyrotropin Releasing Hormone. Or the longer name for it is Thyroid Stimulating Hormone Releasing Hormone, TSHRH. Sometimes you'll see that too. TSHRH.
Wait a second. Let me get that right. TSHRH is another name for TRH. Because what TRH does is stimulate the anterior pituitary to release TSH, or Thyroid Stimulating Hormone.
Thyroid stimulating hormone is released into the bloodstream, where it acts on cells in the thyroid gland to release T3 and T4 thyroid hormones.
So that's the basic hierarchy. And this hierarchy works for most of the other glands of the endocrine system. The hypothalamus releases a releasing hormone that acts on the anterior pituitary, stimulating it to release a stimulating hormone. The stimulating hormone acts on a gland in the periphery, directing that gland to release its hormone.
FSH, Follicle Stimulating Hormone, acts on the ovary on the ovarian follicle, to stimulate the development of a follicle, which is going to release its own hormones, estradiol, progesterone.
Luteinizing hormone also will act on the corpus luteum and stimulate release of hormones. ACTH, Adrenal Corticotropic Hormone. This one we're going to see a few times in upcoming videos.
So ACTH stimulated by CRH from the hypothalamus, or Corticotropin Releasing Hormone, is going to stimulate the adrenal cortex to release cortisol.
So you can look in your book and see the hierarchy, and the names of all of these hormones on your own. And it's probably worthwhile to be familiar with all of the hormones on this page, where they come from, and what they stimulate. Your medical practice will be informed by all of these. You'll see all of these at some point in your medical practice.
A few other hormones to mention are, let's see, the parathyroids. We'll talk about those in another video. The adrenal medulla versus the adrenal cortex. We'll see that in another video.
So the adrenal gland has two parts. And the hormones from each part are very different and distinct. You may recognize norepinephrine and epinephrine. These are the amine hormones from the adrenal medulla. These are involved in the stress response. Whereas the adrenal cortex, which is the other part of the adrenal gland, releases cortisol, also a stress hormone. Aldosterone, which regulates water levels in the body. And also some of the precursors of the androgens in males.
The kidney has its own endocrine function. We covered rennin in another video. And the vitamin D release is considered an endocrine release from the kidney.
The pancreas is an important endocrine gland. And its endocrine secretions are insulin and glucagon. We'll talk about that in another video.
And then, finally, let me mention one other thing. So the pituitary. We've been talking about the anterior pituitary, which stimulates these other glands and tissues to release things. And we'll talk about each one or many of these in other videos.
But the pituitary has two parts. It also has a posterior part. And the posterior part of the pituitary is really neat because it only secretes two things, oxytocin and ADH, Anti-Diuretic Hormone, also known as vasopresin.
And these are pretty neat because they don't require releasing hormones from the hypothalamus. Instead, the hypothalamus is the source of the hormones released in anterior pituitary. So hypothalamic neuroendocrine cells release in the posterior pituitary. And these are released directly into the bloodstream versus the releasing hormones, which are released into local capillaries of the anterior pituitary. And we'll talk about that a little bit more in another video. |
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Term
| Synthesis of Amine Hormones |
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Definition
-Amine hormones are synthesized by a series of enzymatic
modifications of amino acid precursors
-Hormone synthesis takes place in
glandular cells; finished hormones are packaged into secretory vesicles by several mechanisms |
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Term
| peptide hormone synthesis |
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Definition
transcribed from DNA,
translated from RNA,
and often require some
proteolytic cleavage to
make the active form |
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Term
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Definition
Hormone synthesis. We've covered this in another video, but just quickly to remind you, peptide hormones, such as human growth hormone and insulin, are encoded in the DNA, transcribed and translated, are often translated into pre pro hormones that are then cleaved to make their final mature hormone, and then they are secreted from the cells. That's the peptide hormone.
The steroid hormones from the adrenal cortex are cholesterol derivatives. And there are several pathways for making the steroid hormones, starting always with cholesterol, making a product called pregnenolone. And then depending on where in the adrenal cortex the synthesis is taking place, you can wind up with aldosterone cortisol, or the precursors to the sex hormones of the ovaries and testes, the androstenedione, which can make, again, testosterone or estradiol. So the precursors for the androgens are made in the adrenal gland, and then we move on to the sex glands.
And then, of course, the synthesis of amine hormones, such as histidine. Histamine rather. I'm sorry. Made from histidine by a simple enzymatic reaction. And the amino acid tyrosine gives rise to dopamine, norepinephrine, and epinephrine through a series of enzymatic reactions. |
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Term
| Peptide Hormone Processing: Preproinsulin to Insulin |
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Definition
-Preprohormone
targets hormones
to endoplasmic
reticulum for
secretion
-Prohormone is inactive. Cleavage
within secretory vesicles activates
and makes the mature hormone.
-C-peptide is the waste
product produced by
cleavage of proinsulin. It is
secreted with insulin and
excreted by the kidney but
it has a longer half-life and
is useful as a measure of
diabetic progression. It is
measurable by blood test. |
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Term
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Definition
This is an example of the so-called pre pro peptide hormone processing. So this is pre pro insulin to insulin. And, again, insulin is encoded in a gene. We have transcription and translation. But the translation gives you initially this large pre pro insulin, which is not active. The pro hormone is not active.
It needs to be cleaved several times within the secretory vesicles before it can become the active mature hormone. And you can see that first a small signal sequence is removed. And then the C-peptide, the larger C-peptide is removed.
And the C-peptide is a waste product. It actually can be measured. It has a longer half life actually. And it actually is a useful blood test sometimes to understand if insulin is being produced, because you'll find it in the blood for longer than you'll find actual insulin.
And then, finally, here's your mature insulin, which can go out and help cells take up sugar and use it. |
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Term
| Examples of Peptide Hormone Processing: POMC to ACTH |
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Definition
This is an example of a multihormone
protein that is
proteolytically cleaved to
provide many important small
peptide hormones.
POMC: pro-opiomelanocortin
The cleavage of this protein
can provide ACTH, MSH, and
beta-endorphin. |
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Term
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Definition
Another example of a peptide hormone processing that's pretty neat and worth taking a moment on is the so-called POMC to ACTH. So POMC is a gene product. It's actually several pre pro hormones. It's kind of neat. It's pro-opiomelanocortin. So the gene is transcribed and translated. So this is a translation product. This is a protein, a translation product that then gets cleaved into a number of different smaller products.
So it ultimately winds up being ACTH, which is adrenocorticotrophic hormone. This is going to stimulate cortisol secretion by the adrenal glands that makes a lipotropin.
It can make melanocyte stimulating hormones. And it can make beta endorphin, which is one of the endogenous opiates.
And it's kind of neat, because this product of POMC is made in the skin where the melanocyte stimulating hormone can stimulate melanocytes to make melanin. |
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Term
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Definition
And there are some people who think-- and there's some evidence for this. It's still fairly new. And it's interesting. Not totally compelling yet, but interesting. But there are people who have developed some models where people may become addicted to tanning beds, because as they lay in the UV light to stimulate their melanocytes to make melanin and tan, part of that they're making the melanocyte stimulating hormones from POMC. But one of the other products they're making in their skin is beta endorphin. And so there's actually some evidence that people may become addicted to tanning, because they're creating opiates while they're doing it.
And there are some studies. People have used naloxone to try to block people's excessive use of tanning beds. And there's been some interesting results. Again, not totally compelling, but kind of interesting to think about. |
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Term
• Hormone receptors are expressed on the
“target” tissues of hormones |
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Definition
• Membrane receptors that activate second
messengers
• Steroid hormone receptors that activate gene
expression directly |
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Term
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Definition
Hormone receptors. We've talked a little bit about these already in an earlier video. We have basically membrane receptors, the sort of classical receptors that activate second messengers, and the steroid hormone receptors that activate gene expression directly.
Here is a receptor that can interact with G proteins as a G protein linked receptor. When it binds to its hormone it can activate adenylyl cyclase. And that can activate protein kinases that begin a cascade of signaling. |
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Term
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Definition
| Phospholipase C is the other mechanism that we often see associated with hormone activity, where IP3 is produced and calcium gets released from the ER. |
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Term
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Definition
Tyrosine kinase receptor. So growth factors typically bind, or often bind to tyrosine kinase receptors. And insulin is one such growth factor which is an endocrine hormone.
So the insulin receptor is two subunits of tyrosine kinase that when insulin binds to two adjacent subunits of the receptor, they also bind to each other through a disulphide bond. That brings together these two tyrasine kinases. They auto phosphorylate. And then they begin phosphorylating other substrates and begin a signal pathway. |
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Term
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Definition
And again, I think I went over this in an earlier video as well. But here is an example of a steroid hormone receptor that has a hormone binding site and a DNA binding site.
And so it picks up a steroid hormone at the membrane, the cell membrane, and carries it to the nucleus to alter gene expression. |
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Term
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Definition
And thyroid hormone receptors are similar. Although thyroid hormone is not a steroid. It's more complicated. And we'll look at thyroid hormone in another video so you can see its structure.
And this is just a picture of the steroid hormone, the classical steroid hormone activity, where the steroid hormone receptor, when it's bound to a steroid hormone, is translocated to the nucleus, where it acts on DNA to alter gene expression. |
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Term
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Definition
| As I said in earlier videos, the endocrine system is hierarchical. We've seen this before in an earlier video where the top of the hierarchy is the hypothalamus, which releases the so-called releasing hormones. These can stimulate cells in the anterior pituitary gland to release stimulating hormones, which then go through the general circulation to stimulate glands in the rest of the body to release whatever hormone product they are releasing. The other thing that the hypothalamus can do is it can send axons directly into the posterior pituitary and release a couple of hormones systemically as well. |
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Term
| endocrine vs neuroendocrine and hormone delivery |
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Definition
- Endocrine
• Most common
(classical) mode,
hormones delivered to
target cells by blood
- Neuroendocrine
• Hormone is produced
and release by a
neuron, delivered to
target cells by blood |
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Term
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Definition
In the endocrine system, we can talk about two different kinds of cells that release hormones. One is the classical endocrine cell. This is the most common, so, of the endocrine system.
Endocrine cells are modified epithelial cell that can release hormones. They make some hormone shown here. We have three different types of endocrine cells making three different types of hormones. And they release those hormones into a capillary where they join some vascular system, either locally or globally, and act on a target cell that some distance away from the original endocrine cell that release the hormone.
The other mechanism of release in the endocrine system is the neuroendocrine release. And neuroendocrine cell is a neuron that is stimulated by other neurons to create an action potential. And when its action potential reaches its terminus, instead of releasing neurotransmitter, the neuroendocrine cell releases hormones into a bloodstream. And those hormones travel to some distant target where they have their effect.
In the hierarchical system of the endocrine system, the neuroendocrine cells are in the hypothalamus. The endocrine cells are in all the other glands. |
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Term
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Definition
These pictures show us a little more anatomy of the brain and the pituitary gland. So if you've done your neuroanatomy, you know that this is the corpus callosum, and the lateral ventricle. And this is the third ventricle, this area in here. And the floor and walls of the third ventricle, you may remember from neuroanatomy, are the hypothalamus. That's where the hypothalamic neurons live.
And so we can go down into this picture, and we can see a little larger, a little bit more magnified view of part of the hypothalamus. And so this tissue is dotted with little areas where there are neurons that have various functions that you can ascribe to the hypothalamus. Many of the neurons of the hypothalamus are neuroendocrine cells whose axons travel into this stalk called the infundibulum. And the infundibulum is the stalk between the hypothalamus and pituitary gland.
And this is the pituitary gland. The pituitary gland is sitting down in the bone, in a little-- in the sphenoid bone, in a little indentation you may have seen in anatomy called the sella turcica. It's often a useful landmark radiologically. And also in gross anatomy, they usually try to show it to you if they can. So the hypothalamus is sitting here above the sphenoid bone. It's got axons traveling down to the infundibulum and down into the pituitary gland.
Now, we're going to think about the pituitary gland as having two parts. It has an anterior component and a posterior component. Anterior is here. And posterior is here.
And we can go over here, and we can see it again a little bit more clearly-- anterior or adenohypophysis is the other name for the anterior pituitary. So I'll just write above that, anterior pituitary. And the neurohypophysis is the posterior pituitary.
And you may have heard things referred to as hypophyseal. That means they're referring to the pituitary. So the hypophyseal stalk is another name for the infundibulum.
So again, so the anterior and posterior parts. And we can see just from this picture that we're looking at, that there are some differences between the two. And the differences are that in the anterior, we have lots of endocrine cells. These are endocrine cells that secrete hormones directly into these capillary beds. So we have endocrine cells secreting hormones right into these capillary beds.
However, to stimulate their release, we have to have some hypothalamic neuroendocrine cells that release enzymes into the infundibular capillary beds. So we see that there are special beds of capillaries in the infundibular stalk or the hypophyseal stalk. And this is where hypothalamic neuroendocrine cells release they're releasing factors. The releasing factors then travel around through these capillaries down into the anterior pituitary, where they stimulate anterior pituitary endocrine cells to release stimulating factors.
We'll see a diagram. Well, actually we have it right here. So let's look at an example of this. So, I think in an earlier video, we talked about the thyroid. Here's the thyroid, a stimulating hormone.
So in the hypothalamus, there is a TRH neuroendocrine cell. Let's say it's here. And it releases TRH here in infundibular stalk. So TRH would be released here.
This is a little hard to see, I think. TRH would travel locally to the anterior pituitary and stimulate the release of thyroid stimulating hormone from a pituitary endocrine cell. That thyroid stimulating hormone would go into the general circulation where it could get to the thyroid gland and stimulate the thyroid gland to release thyroid hormones.
The other kind of neuroendocrine cell in the hypothalamus is the type that directly projects its axon into the posterior pituitary and releases its hormones directly into the general circulation in the posterior pituitary. The only two hormones that are released in the posterior pituitary in this way are anti-diuretic hormone which acts on the kidneys to retain water, and oxytocin, which stimulates the uterine smooth muscle and mammary glands during reproductive events.
The rest of the hormones that are regulated by the hypothalamus are regulated by the anterior pituitary in this hierarchical system that involves a releasing hormone and a stimulating hormone via the infundibular stalk, specialized capillaries in the infundibular stalk, which which will get the releasing hormones from the hypothalamic neuroendocrine cells and take those releasing hormones to the anterior pituitary, stimulating an endocrine cell to release stimulating hormone, which goes into the general circulation and stimulates a gland. |
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Term
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Definition
Here's another picture just so that you can see it in a slightly different way. I think it's always useful because some of these anatomical cartoons can be hard to see. And it's a little hard to visualize.
So again, here's a hypothalamic neurosecretory or neuroendocrine cell-- neuroendocrine cell-- releasing a releasing hormone in the infundibular stalk into the capillaries of the infundibular stalk. These travel into the capillaries of the anterior pituitary where they stimulate endocrine cells of the anterior pituitary to release their own hormones, which then go into the general circulation. Posterior pituitary, there are neuroendocrine cells of the hypothalamus that have axons that actually travel into the posterior pituitary and release oxytocin or anti-diuretic hormone directly in the posterior pituitary. |
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Term
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Definition
Growth hormone and somatostatin
• Thyroid hormones
• Parathyroid hormone and vitamin D
• Endocrine pancreas
• Adrenal hormones
• Cortisol and behavior |
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Term
| Effects of HGH -induced IGFs: |
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Definition
•Increases blood glucose
and insulin
•Increases lipolysis
•Increases protein synthesis
•Increases growth of lean
body mass (muscle and
bone) |
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Term
|
Definition
dwarfism,
delayed puberty, obesity |
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Term
|
Definition
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Term
HGH secretion stimulated by
GHRH
Three forms of negative
feedback on HGH: |
|
Definition
1. GHRH feeds back on the
hypothalamus
2. IGFs feed back on the
anterior pituitary
3. IGFs stimulate somatostatin
release from the
hypothalamus to inhibit
HGH release |
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Term
|
Definition
So we have videos coming up on thyroid and pancreatic hormones. But we don't have any specific video on growth hormone and somatostatin. So I thought it would be useful to put that in here. These are important hormones, again, that are coming from that hypothalamic pituitary hierarchy. And they're really important in growth in early life, so I think worth a look.
So the hypothalamus secretes growth hormone releasing hormone. And it also releases somatostatin. And these two hormones released by the hypothalamus, these are released into the infundibulum stalk capillaries. And they're going to be stimulating or acting on cells in the anterior pituitary. But they have sort of opposite effects.
So growth hormone releasing hormones stimulates the anterior pituitary to release growth hormone, human growth hormone, HGH. You hear about it during the Olympics a lot. And sometimes people use it to try to develop more muscles for sports. But it's very important in development. Growth hormone is released by the anterior pituitary, where it goes and works on target-- all tissues, basically, are responsive to growth hormone at some level. But certainly muscle and bone are very responsive during childhood.
They create these somatomedins, which are insulin-like growth factors, which have a negative feedback effect on the anterior pituitary. This helps to keep you from over-expressing a growth hormone or from over-releasing growth hormones. So you have growth hormone released. It negatively feeds back on itself to inhibit its own release a little bit.
But in addition to that-- because you want to have a lot of control if you think about it, especially during childhood, you want to have a lot of control over growth hormone-- you also have hormone from the hypothalamus called somatostatin that inhibits the anterior pituitary from releasing growth hormone. And as target tissues are releasing their somatomedins or their insulin-like growth factors, these can also go and positively feedback on somatostatins. So this is another way that you can inhibit growth hormone effect. This as kind of a neat example of negative and positive feedback regulation in order to regulate very closely the amount of growth hormone that's being released.
What are the effects of human growth hormone? So it's going to increase these insulin-like growth factors that obviously can act on blood glucose and insulin levels. They increase the breakdown of fat for use in energy production.
They increase protein synthesis. This makes a lot of sense because they're a growth hormone. So they're helping us grow. They increase the growth of muscle and bone.
There are deficiencies of human growth hormone, which can result in dwarfism, delayed puberty. And interestingly, obesity can be an issue with human growth hormone because your lean muscle mass isn't growing properly. And there can be excesses of human growth hormone that lead to gigantism and acromegaly. And we see somebody here who's had an excess of human growth hormone.
We've gone over the inhibitory mechanisms. And what we can see here is that there are-- so we saw these-- there's a lot of regulation of growth hormone levels coming from the anterior pituitary. And we can see some of where that comes from.
We can see that levels of growth hormone over the course of a single day are very variable. And there's a lot of variability and a lot of increases and decreases in growth hormone. Obviously during exercise, you want to get a nice boost of growth hormone so you can develop muscles.
Interestingly during certain parts of sleep, we have increases in growth hormone. That's why it's so important that children get their sleep because it's really critical to their proper growth because you can disrupt growth hormone levels by having disrupted sleep. So this just gives you an overview of the importance of the regulation of hormone levels, especially something as important as growth hormone, and a couple of mechanisms by which growth hormone can be regulated. |
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Term
|
Definition
Most thyroid
hormone
released is
T4 (90%)
-T3 can have nongenomic
effects such as
modification of ion
channels. In the heart,
T3 can modify the
activity of intracellular
Ca2+ release channels
to increase the
contractility of heart
muscle (positive
inotropic effect). T3 can
also acutely increase
mitochondrial O2
consumption |
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Definition
The other hormone-- and this is going to be covered in another video in the thyroid section. But I wanted to just mention thyroid hormones, maybe introduce them here because they're kind of unusual. They don't really fall into any of the categories too well. I think technically they're considered an amine because they are derived from an amino acid.
But these are the two major thyroid hormones-- thyroxine and triiodothyronine, sometimes called T4 thyroxine, and T3. And the reason they're 4 and 3 is because the thyroid hormones are modified with iodine. And the iodine in T4, there are four iodines. And in T3, there are three iodines.
The organization of the iodines is important. See, there are two ring structures you need to have in an amino acid, basically the amino acid backbone over here. And the two iodines in T3 need to be near the amino acid.
And you may have already in your clinical experience encountered RT3 or reverse T3. And reverse T3 is simply a version of T3 that instead of having two iodines here has the two iodines on the other ring. It's not active. And it's useful to know if you have reverse T3 because it's not an active form of thyroid hormone.
The thyroid hormones also are really important in growth and metabolism. And we can see some of their effects here. First of all, let me say that T4 is by far the greatest amount of thyroid hormone that's produced. So 90% or so of thyroid hormone that's really is T4.
But the active thyroid hormone is T3. And T4 has to be converted into T3. And cells have an enzyme that will do that. And we see here that even though it's not a steroid, it looks like a steroid in the way it interacts with the receptor. So T3 has a nuclear receptor that's a steroid hormone-like receptor that when it's bound to T3 is translocated to the nucleus and initiates gene expression.
And the gene expression can be related to growth, bone and muscle growth, just like with human growth hormone. It can also be involved in development of the nervous system. It's very important in basal metabolism and increases oxygen consumption in the basal metabolic rate. It helps with glucose absorption, the breakdown of glycogen, the formation and the breakdown of fat, and the formation of new glucose when needed and in starvation. And it has important cardiovascular effects.
So I wanted to introduce thyroid hormone here while we're talking about hormones in general. But we'll see it again. And we'll talk a little more about it in a future video. |
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Definition
So as part of our consideration of the endocrine system, let's take a look at the pancreatic endocrine hormones glucagon and insulin. The pancreas has exocrine hormones as well and exocrine function. This part of its digestive function. It releases many enzymes that are involved in digesting fats and other types of food in the GI tract. But in this video, we're concerned only with the endocrine hormone secretions of the pancreas.
The endocrine pancreas releases insulin, glucagon, and somatostatin. Insulin is released by the pancreas by-- you probably already know this, it's fairly common knowledge-- the beta cells of the so-called islets of Langerhans of the pancreas. And insulin is released in response to food. It's released in response to an increase in blood glucose. That's its major stimulatory factor.
Other things can also increase insulin, however. Any kind of nutrient increase can stimulate insulin release, such as amino acid concentration in the blood going up or fatty acids. Glucagon presence can also stimulate insulin. We'll talk about that a little bit. Cortisol can stimulate insulin.
And so sometimes people who are under a lot of stress may sometimes lose weight. And that's because they are secreting insulin and utilizing their sugar more efficiently. And some other vagal stimulation, some other things can stimulate insulin.
Things that can decrease or inhibit insulin secretion are decreased blood glucose, fasting, exercise, somatostatin, which is secreted by the delta cells of the pancreas. And some activation of some parts of the autonomic nervous system, sympathetic nervous system.
What does insulin do? Well, probably its most well-known function is to increase the uptake of glucose by cells. Cells can't just take up glucose in the blood by themselves. They need insulin to act on them to actually pull the glucose transporter into the cell membrane so glucose can be taken up by the cells.
Insulin also increases glycogen formation. So if you've just eaten, you're going to use some of that sugar right away, some of that glucose right away to fuel whatever activities you're participating in, but you can't use it all. And so the first storage form, the short-term storage form is to make glycogen.
Because insulin is increased when glucose levels are rising from food intake in the blood, it decreases glycogenolysis or breakdown of glycogen. That would make sense because you don't need to break down your glycogen if you're eating. It also decreases gluconeogenesis or the production of glucose from other substrates because you don't need to do that.
It does increase protein synthesis. So it is a pro-growth hormone. And it increases, of course, fat deposition. Because the other thing you do when you have access glucose in your blood that you can't use, and once your glycogen stores are full, glucose is converted into fat for long-term storage. So of course, glucose also decreases lipolysis. It has the opposite effect. It tends to build up fat and not break it down. And it can increase potassium uptake into cells as well.
It decreases blood glucose. That's its probably most important function is to decrease blood glucose. And again, it's after eating.
In fact, in thinking about the stimulatory factors, the things that increase insulin secretion from the pancreas, I remember a study where they actually showed that insulin levels went up in the blood of people who saw pictures of food. So in preparation for eating, insulin can be increased. And I even think one of the pictures that increased insulin was a picture of the McDonald's golden arches. So even just thinking about food can have an impact on insulin secretion.
And we see here this kind of gives us a little bit of a look at the flow of nutrients and the impact of insulin on different tissues. So as blood glucose goes up, one place where you really want glucose to be taken up is in the muscle because that's where your biggest energy expenditure comes from is from the muscle. So insulin can increase glucose uptake for muscle.
It can also increase amino acid uptake. That also makes sense. If you're exercising, even if you're fully grown, if you're exercising, you're building muscle. You're making muscles larger and stronger, so you want to have-- as I said, insulin is pro-growth. So you'd want to have that amino acid uptake.
But of course, if there's excess glucose, you have to store it somewhere. And you can store it in adipose tissue by making fat cells bigger. And insulin tends to drive fat production, not fat breakdown.
And in the liver, we can see here that the glucose in the blood is going to be stored as glycogen. And we see here the black arrow indicates that the insulin is promoting glycogen production, not breakdown of glycogen because you don't need to break down your glycogen if you've had a meal.
And insulin receptor, I think we saw this in an earlier video, but insulin binds to tyrosine kinase receptor. And when insulins are bound to adjacent tyrosine kinase receptors, it pulls them together. And they begin activating substrates, including producing second messenger such a cyclic AMP and IP3, depending on the cell involved. |
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Definition
Glucagon is the other major endocrine pancreatic hormone. And glucagon is released by the alpha cells of the islets of Langerhans. And you can think about it-- the easiest way to think about is it has the opposite effects of insulin.
Glucagon is released in response to fasting. So as glucose levels are going down in the blood, you're getting into a fasting state. You start releasing glucagon to have the effects of increasing glycogenolysis. So you're going to start breaking down your glycogen so that you can make your glycogen into glucose and feed some of your cells that need it.
It increases gluconeogenesis, making glucose from other things like amino acids. It increases lipolysis. So you're breaking down fatty acids now and trying to use those to get some energy to fuel whatever activities you're involved in.
And it increases the formation of keto acids. These are very important because the brain, especially, cannot function on fatty acids. It needs glucose. And in the absence of glucose, it will work with keto acids. So the formation of keto acids are really important in fasting because that's how you keep your brain functioning when there's no glucose around.
Sorry, that's the wrong picture. That's the insulin on nutrient flow. I thought it was the glucagon on nutrient flow. But glucagon would have the opposite effects of insulin, basically. It would start breaking down fatty acids. And it would start breaking down glycogen. But all with the same purpose of providing glucose for your body's activities. |
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Term
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Definition
• Autoimmune destruction
of b cells (type IV
hypersensitivity)
• Hyperglycemia
• Ketogenesis
• Metabolic acidosis (DKA)
• Osmotic diuresis and thirst
• Hyperkalemia
Treatment: insulin replacement |
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Term
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Definition
• Down-regulation of insulin
receptors (a.k.a. insulin
resistance)
• Hyperglycemia
• Osmotic diuresis and thirst
• Hyperkalemia
• Ketogenesis absent or less
than Type I diabetes
• In HHNS, neurological
symptoms, coma, death (no
ketones!)
treatment: activate the secondmessenger
systems normally activated
by the insulin-receptor binding |
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Definition
In this video, I'm going to introduce the adrenal hormones and talk a little bit about the adrenal gland, where the different hormones come from, and then we'll end up with a little bit on the regulation of adrenal hormones, including some interesting behavioral effects of cortisol.
The adrenal gland has two parts with respect to hormones. It has a cortex, which is an outer part. Just like in the brain, the cerebral cortex is the covering of the brain, the cortex of the medulla is the outer part of-- the cortex of the adrenal gland is the outer part of the gland, and the medulla is the inner part. Just again, like in the brain, we have the medulla down below the cortex, we have the medulla of the adrenal gland down below the cortex.
If we cut the adrenal gland into a kind of a wedge and look at it histologically, we can see a little bit more detail of the organization. Here's the medulla, that inner part. And the cortex is actually broken down into several other zones, the zona glomerulosa, zona fasciculata, and zona reticularis. And different hormones come from different parts of the adrenal gland.
So for example, the medullary hormones are the catecholamines-- the dopamine, the norepinephrine, the epinephrine, that are associated with activity of the autonomic nervous system. Cortical hormones from the adrenal glands come in three different types. The mineralocorticoids, which is essentially aldosterone, the glucocorticoids, which is cortisol, and the androgens, which are the precursors to the sex hormones.
And they come from different parts of the adrenal gland. They mineralocorticoids come from the outer part of the cortex, the zona glomerulosa, the glucocorticoids come from the zona fasciculata, and the androgens come from the inner part of the cortex, the zona reticularis. With the mineralocorticoids and glucocorticoids, you can remember that they're cortical because of their names, glucocorticoid. The corticoid refers to the fact that these hormones, cortisol, basically comes from the adrenal cortex, not the adrenal medulla.
Where are the adrenal glands? Well, the name tells you that as well, if you haven't already seen them, ad-- renal. They are just above the kidneys. Renal refers to kidney, ad means near or above. They are near the kidneys, they sit right up on top of the kidneys.
And this is just a picture showing the steroid nature of the adrenocortical hormones. So all have the adrenocortical hormones are steroids. And they are all cholesterol derivatives. Here is a little bit on the synthesis of adrenal steroid hormones. We've seen this in other videos as well. |
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Definition
All adrenal steroids start with cholesterol. And we can see here this refers to the zona glomerulosa, the zona fasciculata, and zona reticularis. So the cortisol creating cells are primarily in the fasciculata, but also sometimes near the border with the reticularis. And the androgen cells can be found mainly in the reticularis, but also sometimes near the border with the zona fasciculata.
And under the control of ACTH, coming from the anterior pituitary, cells of the zona glomerulosa start to turn cholesterol into the precursor pregnenolone. All of these cells can do this. But only the cells in the zona glomerulosa will continue this synthesis to make aldosterone. Likewise, the cells of the fasciculata and reticularis have specific enzymes that can make cortisol, or testosterone, and androstenedione, which can then go on to make testosterone or 17 beta-Oestradiol.
What are the actions of the adrenal corticosteroids? Well, the glucocorticoids, cortisol, has a lot of important functions. It's an important metabolic enzyme and a stress response enzyme. And it's related to arousal in general. And we'll see that in a minute on another slide. So it can do things like increase gluconeogenesis.
So if you have to have some activity, for example, if you're under stress, you're running from a predator, for example, you need to make some quick energy, cortisol can help you produce new glucose from substrates in the body. It will help to break down proteins, which is sometimes what you use to perform some gluconeogenesis. It will help to break down fats, so that you can use fats in your energy production.
And actually, it decreases glucose utilization and sensitivity to insulin a little bit. But again, it's looking for more reliable sources of energy for dealing with stress situations. And it can have some other effects long term on inflammatory and immune responses.
The mineralocorticoids, which is basically aldosterone have effects that we've talked about in videos from our lectures on the kidney. The most important, the increasing, the absorption, or reabsorption and the nephron of sodium, and increasing the secretion of potassium and protons, acids. And then the adrenal androgens become the precursors that the ovaries and testes need to make testosterone and 17 beta-Oestradiol. |
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Term
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Definition
Let's talk about cortisol. Cortisol is one of the stress hormones. So under stress, we have activation of the autonomic nervous system, the sympathetic part of the autonomic nervous system. And the adrenal medulla will release adrenaline or epinephrine norepinephrine.
In addition, however, the adrenal cortex can release cortisol. And it does so under the control of parts of the brain that can interact with neurons in the hypothalamus. So if we go backwards a little bit and we think about our endocrine hierarchy, this is our adrenal cortex making cortisol. The hormone that induces the production of cortisol by the adrenal cortex is ACTH, Adrenocorticotropic hormone. This is released by the anterior pituitary.
The anterior pituitary releases ACTH in response to a hypothalamic hormone called CRH, Corticotropin-releasing hormone. But what makes the hypothalamus release CRH? Well, the hypothalamus is under the control of other parts of the brain, so-called higher centers. So for example, what might you need to release cortisol for?
Let's say you encounter a large, aggressive bear in the woods. You need to escape, you may need to run, or you may need to fight. Your brain, those higher centers of your brain, see what's happening. They perceive what's going on. And they send information to the hypothalamus, saying we need cortisol right now so that we can do things like increase our gluconeogenesis, and lipolysis, and provide some energy for muscles that are about to be heavily stressed.
So that's the interaction between the higher centers and the hypothalamus. I'd like to also point out here, just as a kind of foreshadowing of something we'll see in another slide, is that as the adrenal cortex makes cortisol, that cortisol, of course, is released into the blood like any other endocrine hormone. And it has a negative feedback on both the anterior pituitary and the hypothalamus.
However, what's not shown here is that it also has an effect on some of the higher centers. And we'll look at that again in a few more slides. In the absence of a large angry bear in the woods, we also make cortisol just during a normal day. And we can see that there is sort of a cycle to cortisol.
Cortisol levels go up and down. But they are highest at times when we are probably becoming the most aroused. That is, when we are waking up in the morning until we get to about the halfway point of the morning, early part of the afternoon. That's when cortisol levels are going up. They start to drop as the day goes on. And when we go to sleep, they go to their lowest. So cortisol, increased cortisol levels are associated with increased activity and increased arousal.
What are some of the things that can stimulate cortisol release? Again, in the absence of an angry bear, one is of course decreased blood cortisol. So as cortisol down regulates its own release, its levels go down. That relieves the negative feedback on the hypothalamic and anterior pituitary. And so cortisol will kind of go up and down throughout the day like that.
The sleep-wake transition, as we saw here, is a big, important stimulator of cortisol. Stress, the angry bear in the woods or other kinds of stresses can increase cortisol. Certain types of psychiatric disorders sometimes show with cortisol disturbances, including major depressive disorder, where cortisol regulation can sometimes be impacted. Changes to ADH release. So ADH can stimulate cortisol. And of course, some of the actors in the sympathetic nervous system can also.
Things that can inhibit it, of course, increase blood levels or cortisol is the number one. And opioids can release, can inhibit cortisol. And somatostatin, our friend, the sort of general inhibitory hormone from the hypothalamus and the endocrine pancreas can also inhibit cortisol release. |
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Term
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Definition
Disturbances of the adrenal glands, there are several. Probably the most well known are Addison's disease and Cushing's disease. And I put this here because since you're part of a Yale-based PA program, this is Harvey Cushing, who was a neurosurgeon at Yale, and who named Cushing's disease. In fact, the library at Yale, at the Yale Medical School, is named for Harvey Cushing.
So Addison's disease, this is a lack of cortisol, reduced cortisol levels. And one of the things that we get with that is hypoglycemia. So we start to get low blood sugar levels, and weight loss, and weakness, and hyper-pigmentation. I'm gonna make a little note next to that.
And one of the things that happens when cortisol levels are low is you reduce that negative feedback on the hypothalamus and the pituitary. So let's go back and look at that again. So again, here we are in Addison's disease, where cortisol levels are low because the adrenal gland is not producing enough cortisol. That relieves this negative feedback. And so the levels of ACTH increase in an attempt to try to get more cortisol produced.
And I don't know if you remember, but in one of the other videos that we looked at, we saw that they proopiomelanocortin gene, which has beta endorphin and has several other hormones, one of the hormones that's also produced by the cleavages of the proopiomelanocortin gene, one is ACTH and the other is melanocytes-- or actually three different versions of melanocytes stimulating hormone. And that is why you wind up with a hyper-pigmentation that's characteristic of Addison's disease, because you have an increase in ACTH because of the low cortisol levels, and the increase in the activity and production of the POMC gene products, giving you some hyper-pigmentation.
Cushing's syndrome and Cushing's disease are from excess a ACTH in the face of a normally functioning adrenal gland. And so now you have a lot of ACTH. In Cushing's disease you have a lot of ACTH, and you're making a lot of cortisol. And so now you have a lot of cortisol. In Cushing's syndrome you have an increase in cortisol because of a primary adrenal gland problem. And you have decreased ACTH now.
So you can see that there are two different ways that you can get increased cortisol. One is from an increase in ACTH, which drives the production of cortisol from adrenal. And the other is from an increase in cortisol produced from the adrenal abnormally, which actually gives the decreased ACTH. And the symptoms of the Cushing's disorder, usually one prominent one is hyperglycemia, so it's having kind of the opposite effect of Addison's disease, and obesity.
So it's useful to know Addison and Cushing's disease as a way of thinking about the functions of cortisol. And they're not that unusual, I think, clinically. |
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Term
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Definition
So let's talk a little bit more about the negative feedback or cortisol release. And then we can talk about some fun things that have to do with that. So I told you that as cortisol gets released from the adrenal cortex, it's going to negative feedback on the anterior pituitary and hypothalamus. But it also has a negative feedback effect on some of the so-called higher centers that regulate the hypothalamus.
And some of those are these. The cerebral cortex, the amygdala-- this is a part of the brain that becomes very active during highly aroused situations, especially in situations where fear and anger, or the need to fight, are major components.
And the other part is the hippocampus. So the cerebral cortex and the amygdala stimulate the hypothalamus to release CR-- well, in this picture, it's called CRF, but this is the same thing as CRH. This is Corticotropin-releasing hormone. Sometimes people call those hypothalamic hormones, the releasing hormones, releasing factors, which is why this says RF instead of RH.
So anyway, the cerebral cortex and amygdala stimulate the hypothalamus to release that, which then drives cortisol production by ACTH. The hippocampus of the brain which is a part of the brain involved in emotional regulation and memory formation, actually is stimulated by levels of cortisol in the blood to negatively regulate the hypothalamus.
So as the hippocampus gets these increased levels of cortisol, it starts driving inhibitory input to the hypothalamus and trying to slow down the production of CRH. And so we have two of competing influences on the hypothalamus.
And the way to think about this, I think, is that, if you are really in danger, your cerebral cortex knows that. It's getting that information, it's getting information about something that you really need to be stressed about. And it's feeding the amygdala that information, saying, don't stop running, don't stop fighting, keep going. And this is going to keep telling the hypothalamus keep the cortisol coming, we really need it.
But sometimes you get something happens and you're afraid, and then it's over and you need to relax. And the hippocampus is working on that angle. The hippocampus is saying, OK, just relax now, everything's OK. If it's not really OK, the cerebral cortex and amygdala will override it. So it's not a problem.
But when it is OK, you need to relax. You don't want to have cortisol all the time. So the hippocampus is the one that's telling the hypothalamus to slow down and stop the cortisol release. So what's fun about this is that-- we all know people who, some people, something bad happens, and they are ready, and they act, and then it's over, and they can just kind of move on. |
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Term
Cortisol and behavior
• Regulation of receptor
number
• Up- vs. downregulation
• Lick Your Rats |
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Definition
And then we know other people who something bad happens, and they cannot stop worrying about it, they can't relax, right? And so something that came out of some literature a number of years ago in rats actually may have some bearing on this in human beings. And it's pretty neat.
So somebody, this was probably in the 1960s, some researchers noticed that mother rats when their babies are born, they often will lick them immediately. So this is important in rodents, and actually in a lot of mammals, there's a lot of interaction right away with newborns. But mother rats often lick their babies a lot.
But some rats don't do that. Some mother rats leave their babies alone and they're kind of neglectful, is the word that's used. But it's not necessarily neglectful, but that's the word people use. They don't like them. They don't interact with them very much.
And the researchers found that rat pups who were raised by mother rats who didn't lick them a lot when they were first born had trouble regulating their cortisol levels after experiencing fearful stimuli. They couldn't turn cortisol off. Whereas baby rats who were raised by mothers who did a lot of licking and grooming in the early hours of life, those rats were able to manage fearful stimuli much better and were able to shut off their fear responses more quickly after they were exposed to something frightening.
So this turned into actually a pretty big area of research. And it was found that the level of cortisol receptor expressed by neurons in the hippocampus is influenced by early life experience in rodents. And if you go to the website that will be shown on the next slide, called "Lick your Rats," you can actually see how this happens.
So the licking and grooming of the rat pups early in life changes the DNA so that it's an epigenetic modification of the DNA. It actually opens up the DNA around in hippocampal neurons, around the cortisol receptor gene, and makes it easier to express that gene. So rat pups who are licked and groomed often and early in life express more cortisol receptor in their hippocampal neurons than the other rat pups do.
And in humans, there's some evidence that something similar may actually be going on. A study was done-- it's pretty hard to figure out what's going on in a hippocampal neuron from a human who is alive. A study was done in people who had committed suicide.
And what they found was they went into the brains and took some hippocampal neurons and looked at the epigenetic modifications to the cortisol receptor gene, and found that in those folks there were differences in the level of expression of that cortisol receptor gene that could be explained by early traumatic life experiences.
And so there was a relationship between those. So I encourage you to go to "Lick your Rats." Again, the website link will be shown in the next slide. And you can actually sort of simulate licking a baby rat and you can watch the DNA being modified as you do so. It's kind of neat to see it. |
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