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Transcribed by Leslie Afable 4/24/14 Organ Systems Lecture 40– Histology of the Endocrine System II by Dr. Elisabeth Lopez Slide 65 – Adrenal Glands Dr. Elisabeth Lopez – OK let’s start up again for the second half. So at the very end this lecture, there is a flow chart style review slide that shows something that I want to emphasize now before we go on. For a lot of the hormones acting on the endocrine glands or secreted by the endocrine glands, a very common pattern is that there is a releasing hormone released by the hypothalamus, which then acts on the anterior pituitary and then the anterior pituitary will secrete hormones to act on other organs. So, for example, there will be like a prolactin-releasing hormone from the hypothalamus acting on the cells of the anterior pituitary which then releases prolactin. Or the hypothalamus has TSH- releasing hormone to tell the anterior pituitary to release TSH and that acts on the thyroid to release T3 and T4. That’s just a pathway that you should realize exists. For the adrenal glands, I mentioned that because the anterior pituitary will release ACTH, which is a hormone from the pituitary that acts on the adrenal cortex to tell the cells of the adrenal cortex to release their own hormones. But we’ll see it at the very end, there’s a summary slide. So adrenal glands now. Slide 66 – Adrenal (Suprarental) Glands Dr. Elisabeth Lopez – So here is what the adrenal glands look like. They sit on top of your kidneys. So that’s where it gets the name ADRENAL. “AD” means above and “RENAL” means kidney. They aren't symmetrical, they are different shapes so the LEFT one is kind of semilunar-curved shaped and the RIGHT is more of a triangle or a wedge. Slide 67 – The Gland is Divided into 2 Histologically and Functionally Different Regions: Dr. Elisabeth Lopez – If you cut them, so if you cut them sagittally like here or here and look at the cross section you can see different areas. The outer part is the CORTEX 1

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Page 1: 40: Endocrine II

Transcribed by Leslie Afable 4/24/14

Organ Systems Lecture 40– Histology of the Endocrine System II by Dr. Elisabeth Lopez

Slide 65 – Adrenal GlandsDr. Elisabeth Lopez – OK let’s start up again for the second half. So at the very end this lecture, there is a flow chart style review slide that shows something that I want to emphasize now before we go on. For a lot of the hormones acting on the endocrine glands or secreted by the endocrine glands, a very common pattern is that there is a releasing hormone released by the hypothalamus, which then acts on the anterior pituitary and then the anterior pituitary will secrete hormones to act on other organs. So, for example, there will be like a prolactin-releasing hormone from the hypothalamus acting on the cells of the anterior pituitary which then releases prolactin. Or the hypothalamus has TSH-releasing hormone to tell the anterior pituitary to release TSH and that acts on the thyroid to release T3 and T4. That’s just a pathway that you should realize exists. For the adrenal glands, I mentioned that because the anterior pituitary will release ACTH, which is a hormone from the pituitary that acts on the adrenal cortex to tell the cells of the adrenal cortex to release their own hormones. But we’ll see it at the very end, there’s a summary slide. So adrenal glands now.

Slide 66 – Adrenal (Suprarental) GlandsDr. Elisabeth Lopez – So here is what the adrenal glands look like. They sit on top of your kidneys. So that’s where it gets the name ADRENAL. “AD” means above and “RENAL” means kidney. They aren't symmetrical, they are different shapes so the LEFT one is kind of semilunar-curved shaped and the RIGHT is more of a triangle or a wedge.

Slide 67 – The Gland is Divided into 2 Histologically and Functionally Different Regions:Dr. Elisabeth Lopez – If you cut them, so if you cut them sagittally like here or here and look at the cross section you can see different areas. The outer part is the CORTEX and the inner part is the MEDULLA. So this is a magnification. On the outside you have a capsule and then here is the cortex that is bigger than the medulla. The cortex will have 3 layers and then the medulla is deep to that. It’s symmetrical so you will have cortex all the way around the top and bottom and sides and the medulla in the center.

Slide 68 – Development of the Adrenal GlandsDr. Elisabeth Lopez – Like some of the other organs that we've seen already, the Adrenal glands come from 2 different embryological origins. So this is a cartoon cross section through an embryo. So this is the dorsal side, here’s the neural tube with neural crest cells. So review where they come from if you need to. Here is your gut tube with ..most of the rest of this will be mesoderm. The neural crest cells will migrate down to be various things so DRG, sympathetic ganglia, stuff like that.

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Page 2: 40: Endocrine II

Transcribed by Leslie Afable 4/24/14

Slide 69 – Development of the Adrenal Glands: Neural crest cells from sympathetic ganglia continue to migrateDr. Elisabeth Lopez – They will also migrate down to where the adrenal glands are developing. So here is your neural tube, the neural crest cells have migrated down. So in this particular picture, this is supposed to be migrating down to be part of the sympathetic ganglia down here. Then some of them will continue to migrate ..so here they’ve migrated down to be part of the sympathetic ganglia. Continue to migrate down to where the medulla is developing. So you’ll have neural rest cells surrounded by mesoderm. The neural crest cells will develop into the MEDULLA, so the center part of the adrenal gland. The mesoderm which surrounds it will develop into the ADRENAL CORTEX.

Slide 70 – Adrenal Cortex and Adrenal Medulla are Both Endocrine in Function but They Have Different Embryonic Origin and Perform Different RolesDr. Elisabeth Lopez – So even through these are both part of the adrenal gland, the cortex and the medulla, they're re very different. They come from different embryological tissues and they have different functions. The cortex is from mesoderm and the hormones produced are going to be steroids and the cells will secrete steroids in response to ACTH. The medulla comes from neural crest cells. It’s going to create catecholamines so EPINEPHRINE and NOREPINEPHRINE and that’s NOT in response to ACTH but to STRESS. So like the fight or flight response is the stress causing release of catecholamines.

Slide 71 – Adrenal CortexDr. Elisabeth Lopez – So again, here the picture of the magnified slice of the adrenal gland. Capsule is on the outermost layer and the cortex is right below that and you have 3 layers to the cortex. The outermost layer of the cortex is called the ZONA GLOMERULOSA and then you have the ZONA FASCICULATA and then the ZONA RETICULARIS. All 3 of those are cortex and then below that you have the adrenal medulla.

Slide 72 – Zona GlomerulosaDr. Elisabeth Lopez – So we’ll go through all 3 layers of the adrenal cortex. So outermost if the zona glomerulosa and that is going to release ALDOSTERONE. The cells in there are going to be pretty small cells arranged in cords so that means little stacks of cells or round-ish clusters. They are going to be pretty small and darkly stained and a little acidophilic and they secrete aldosterone and deoxycorticosterone. These hormones are going to control electrolyte balance in the body and fluid balance in the body so they are going to work with the kidneys. They are going to affect the renal tubules to affect the fluid balance.

Slide 73 – Untitled Slide

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Page 3: 40: Endocrine II

Transcribed by Leslie Afable 4/24/14

Dr. Elisabeth Lopez – Here is a picture of it. It’s actually only going.. ..so here is the cortex up here. The zona glomerulosa only goes from here down to here (yellow line). You can see that the cells are arranged in these CIRCULAR patterns and they’re small and darkly stained. One thing you can see if you zoom out a little bit is that the layers alternate in how they look. So it goes from dark to light to dark to light, all relative to one another. But you can definitely see where one layer transitions into the other. The zona fasciculata is the next layer down. That’s this.

Slide 74 – Zona FasciculataDr. Elisabeth Lopez – It’s a very tall layer so most of the cortex is the zona fasciculata. The cells are called spongeocytes because they have little fat droplets inside the cell. So when they are prepared for histology they appear kind of spongy. They are lighter in color because of that and instead of being arranged in little round groups like the zona glomerulosa, they are arranged in COLUMNS. You’ll see lots of capillaries in this layer and this layer produces cortisol and corticosterone. These hormones control general metabolism in the body and have anti-inflammatory effects. And again, this is in the cortex so these hormones are produced in response to ACTH.

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Page 4: 40: Endocrine II

Transcribed by Leslie Afable 4/24/14

Slide 75 – Untitled Slide

Dr. Elisabeth Lopez – So this layer is going to go from up here to down here (blue line). The cells are LARGER & LIGHTER. You can’t really see it at this magnification but you might see little empty looking areas where the lipid droplets used to be before it was prepared and stained. The cells arranged in COLUMNS instead of in round groups.

Slide 76 – Zona Reticularis Dr. Elisabeth Lopez – The next layer down is called the ZONA RETICULARIS. It’s relatively narrow and it secretes ANDROGENS. So DHEA and ANDROSTENEDIONE. So these are going to be precursor cells to sex hormones such as testosterone and estrogen. They will have lipid droplets but not as many so they are darker in color than the previous layer. They are going to be arranged in cords so they’re not going to be arranged in columns but they are arranged in longitudinal groups that might branch a little.

Slide 77 – Untitled Slide

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Page 5: 40: Endocrine II

Transcribed by Leslie Afable 4/24/14

Dr. Elisabeth Lopez – So lets look at that. So down here they are in cords. So this would be cord and this would be a cord here. So the cells go from kind of small to large to smaller again and round clumps to columns to cords. The physiology lectures that Dr. Schiff will give will focus a lot of on the adrenal cortex so make sure you know the layers by name, by where they are and by what they do and what hormones they have. One thing that helps me remember is that the glomerulosa layer is involved in fluid retention and electrolyte balance so that’s kidney stuff and there are glomeruli in the kidneys, and this is called glomerulosa so that helps me remember it’s involved in kidney function. And they are all stimulated by ACTH.

Slide 78 – Adrenal Medulla: Functions as a Modified Sympathetic GanglionDr. Elisabeth Lopez – The adrenal medulla is deeper than the cortex. So in this picture, here is the cortex up here and the medulla is in purple. It’s kind of interesting because it’s basically just a sympathetic ganglion except it doesn’t have post ganglionic axons. It has 2 cell types -- CHROMAFFIN cells which are modified sympathetic neurons and they don’t have axons so they just release their neurotransmitters basically into the bloodstream. So those are the hormones that are produced here EPINEPHRINE and NOREPINEPHRINE. Throughout you will also see GANGLION CELLS which look more like typical neuron cell bodies but mostly you’ll see these chromaffin cells.

Slide 79 – Chromaffin Cells Dr. Elisabeth Lopez – So here I don’t even see any ganglion cells off the top of my head in this picture. So they are all chromaffin cells (CC) arranged in little clusters. Over here are chromaffin cells, they don’t look like typical neuron cell bodies. They are named “chromaffin” because the way you stain them with chromic acid, they stain dark. Each of these cells will either release epinephrine or norepinephrine. Down here these look like neurons and these are the ganglion cells. But the MAJORITY of cells will be chromaffin cells.

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Page 6: 40: Endocrine II

Transcribed by Leslie Afable 4/24/14

Slide 80 – Physiological Effects of CatecholaminesDr. Elisabeth Lopez – So what happens is that the functionally pre-ganglionic sympathetic neurons will release ACh (acetylcholine) in the adrenal medulla. That will induce the chromaffin cells to release catecholamine and that means epinephrine or norepinephrine and that will go to, instead of going to another neuron or to a muscle or something, the epinephrine or norepinephrine will go into the blood to flow throughout body. This will give you the typical flight or fight response. So like increased blood flow to certain organs and increased heart rate and anything you think a sympathetic neuron would do, this would do as well EXCEPT it’s going to be a more long acting effect and a systemic effect. Norepinephrine is more likely to be released if your fight or flight is more from EMOTIONAL STRESS. Epinephrine is more likely to be released if it’s PHYSICAL STRESS.

Slide 81 – Pineal GlandDr. Elisabeth Lopez – And finally the pineal gland. This is going to be located in the brain, in the midline of the brain.

Slide 82 – Pineal Gland; Pineal Body of EpiphysisDr. Elisabeth Lopez – So let’s see if we can see it here. Back here, so here is the front of the brain and the back of the brain and here is the pineal gland right here. It’s in the back of the 3rd ventricle. So here’s the third ventricle (red line), you can’t really see it on the smallest picture. It is going to help regulate your circadian rhythm. It is photosensitive except it’s totally inside your head so it’s not actually going to receive any light. But if it could receive light, it could react to that. Here it is more magnified here. Oh, because it is derived from the brain, it is embryologically from neuroectoderm just like the posterior pit.

Slide 83 – Pineal Gland has 2 Major Cell TypesDr. Elisabeth Lopez – Most of the cells in it.. here is just a histological image of the pineal gland. Most of the cells are called PINEALOCYTES, they are the active cells. You will also have GLIAL CELLS there as well called INTERSTITIAL CELLS but there are relatively few of those.

Slide 84 – PinealocytesDr. Elisabeth Lopez – So you can see in this image it’s going to have these processes here. Those cytoplasmic extensions are going to end on capillaries to secrete the product into the bloodstream. Pinealocytes are going to secrete melatonin and that’s the hormone that’s going to help regulate your circadian rhythm/your day and night cycle.

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Page 7: 40: Endocrine II

Transcribed by Leslie Afable 4/24/14

Slide 85 – Interstitial (Glial) Cells

Dr. Elisabeth Lopez – Here is an image of them. So the active cells, the pinealocytes, are these and they will have bigger nuclei than the other cells in the area. You can’t see the cytoplasmic extensions here because we don’t have enough magnification. The other cells, you’ll see that are relatively RARE are the glial cells, the interstitial cells. So here is one here, this looks like one too (circled in red), you’ll have smaller nuclei and denser nuclei. Those will just act as GLIAL CELLS to the pinealocytes.

Slide 86 – Pineal Gland is Characterized by the Presence of Concretions of Calcium and Magnesium SaltsDr. Elisabeth Lopez – The kind of strange thing about the pineal gland is that over time you’ll get calcium concretions inside the pineal gland just with age and so you can see them here. They are called BRAIN SAND because it’s just like little aggregations of calcium and magnesium salts that are hard and rocky and feel like sand, or would if you could touch them. They don’t do anything and it’s not bad or anything they just accumulate with age. But they’re clinically relevant because you can see them in X-rays and since the pineal gland is right in the midline of your brain, you might see the radio-opaque brain sand right in the midline of your brain. So you can use it as a landmark for if you are in the midline or not.

Slide 87 – Melatonin, Synthesized from Tryptophan by Pinealocytes and Released at NightDr. Elisabeth Lopez – So the pineal gland secrets melatonin. It inhibits GROWTH HORMONE and it’s released at night so it’s released in response to the lack of light going into your retina. Some people think it helps you with jet lag because maybe eating melatonin will help you re-regulate your day/night cycle but I don’t know how much evidence there is for that.

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Page 8: 40: Endocrine II

Transcribed by Leslie Afable 4/24/14

Slide 88 -- Histophysiology of the Pineal GlandDr. Elisabeth Lopez – So since the pineal gland is inside your brain, it can’t get light directly. The information about whether you are seeing light or not comes in through your retina and goes to the suprachiasmatic nucleus and then that information will go to the pineal gland. When norepinephrine acts on the pineal gland, melatonin is released. Melatonin is released when it’s DARK OUT and is INHIBITED when it’s LIGHT OUT, or at least when your eyes perceive light and dark.

Slide 89 – Untitled Slide

Dr. Elisabeth Lopez – So this is kind of the pathway. Is it light or dark outside? That will go to your retina to go to the suprachiasmatic nucleus which will eventually get to the superior cervical ganglion and go back to your pineal gland and that will secrete melatonin.

Slide 90 – Review (Endocrine System)Dr. Elisabeth Lopez – So now this half I finished up really early. Study this flow chart. This is just an overview of the endocrine system. Keep in mind that the endocrine system, even though the hypothalamus isn't in the endocrine system, the hypothalamus controls a lot of the things in the endocrine system. The hypothalamus controls and makes releasing factors for the pituitary OR secretes it’s hormones in the POSTERIOR PITUITARY and then a lot of these hormones act on these other glands.

Slides 91 & 92 – TablesDr. Elisabeth Lopez – This table has all the glands that we talked about today, with some bonus like the pancreas and the gonads, with their hormones what they do and how they’re regulated. So it’s a little summary there. Let me know if you have any questions. Otherwise, we’ll get out a little early.

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