Appendix 3: Communication Hormones Podcast Transcript

Hey guys it’s Sydney and Hanna. Thanks for tuning in again. We’re going to be talking about the communications hormones unit.

First we’re going to talk about negative and positive feedback, which are key concepts for this unit. Negative feedback is how our bodies maintain a homeostatic level of a hormone. I like to think of it as the body saying we have lots of a hormone, so a signal is sent so the body stops making it. Positive feedback is less common, but it’s when multiple steps happen to produce a hormone and then hormone can feedback to stimulate a step to produce more of itself, so it amplifies itself. You’ll see a practical example of this concept when we talk about sex hormones, so keep it in mind.

Before we talk about calcium, I want to talk about parathyroid hormone, which we will refer to as PTH. PTH is a peptide hormone, which means it is non lipid soluble, so you can call it non-lipid soluble hormones or NLS hormones. Remember that an NLS hormone can be made ahead of time and stored, and that it needs to bind to a membrane receptor. The concentration of Calcium ions in plasma is what regulates PTH levels in the body. PTH is released from chief cells in the parathyroid gland, and these chief cells have receptors for calcium ions. If we think back to our communication principles unit, we know that a ligand binds to a receptor to activate a G-protein, to signal to a secondary messenger to stimulate a pathway which will ultimately release PTH.

Now we’re going to discuss calcium regulation in the bone. So in bones, there are osteoblasts and osteoclasts. Osteoblasts form bone, while osteoclasts reabsorb bone. You need to remember that when you hear reabsorbing bone, it means reabsorbing calcium and phosphate from the bone back into the blood. This means that reabsorbing is essentially breaking down bone. To regulate calcium, if blood calcium levels are low, the hormone PTH will bind to membrane receptors on bone which will increase the osteoclast activity, which will increase reabsorption, which we now know means more breakdown of bone, so calcium levels in the blood will increase. An increase in 1,25-OH2-D, which we will talk about soon, will have this same effect on bones.

The professor may mention this in class but I think it’s really cool. We can think about how calcium levels in the blood are always prioritized over bone. An interesting practical example to remember that is that pregnant women need to increase their calcium intake because a fetus uses more calcium. If they don’t increase this intake, the calcium will constantly be coming from bone reabsorption. This will cause brittle bones in the pregnant woman.

A difficult concept to remember is that when there’s low plasma calcium, PTH and 1,25-OH2-D will stimulate the bone to breakdown by osteoclasts to release more Ca, but this breakdown also releases phosphate. The same trend happens in the small intestine, in which 1,25-OH2-D causes the small intestine to increase calcium and phosphate absorption which increases plasma levels. These responses are crucial to increase calcium levels when they drop, however our body doesn’t want phosphate levels to rise too. This is where the kidney comes in and saves the day, because when PTH and 1,25-OH2-D stimulate the kidney, it will increase phosphate excretion which will drop the phosphate blood levels in our blood back down, and it will decrease calcium excretion, so if we excrete less, more stays in our body and the plasma ca levels will increase.

When plasma calcium levels are brought back up, we see negative feedback that goes back to PTH. So if plasma calcium is high enough, they’re going to tell PTH that plasma calcium levels don’t want to be increased any more and PTH levels will decrease.

Another important thing to remember for calcium regulation is that 1,25-OH2-D acts on the kidney, bone and small intestine, while PTH only has influence on the kidney and bone, because they have PTH receptors. When we first talked about PTH, we said it was a non lipid soluble hormone, which means that it needs a membrane receptor. Since the small intestine doesn’t have these receptors, PTH has no effect on it.

We keep talking about 1,25-OH2D, so I’m just going to explain how it’s formed. Vitamin D enters the body from food or the sun which is changed in the liver to 25-OHD, which travels through blood to the kidney. The kidney is where we see that PTH stimulates a hormone called 1-alpha-hydroxylase which converts 25-OHD into 1,25-OH2-D, which has an effect on the kidney, small intestine and bone to increase plasma calcium levels.

When thinking about blood glucose regulation, trying to differentiate between glycolysis, glycogenesis, gluconeogenesis, lipolysis and lipogenesis it can be very overwhelming and confusing. I like to look at what different segments of the words means. Remember that “lysis” means “breakdown”, “genesis” means “formation” and that “neo” means “new”. Also remember that “glyco” and “gluco” refers to glucose and “lipo” refers to fats.

For example, I will break down the word gluconeogenesis- gluco means glucose, neo means new, and genesis means formation. If we put these fragments together we get the formation of glucose from something new, something new meaning amino acids, glycerol or lactate. If we think about this in terms of glucose regulation, we know that the process would be stimulated by glucagon because we would want to build more glucose if blood glucose levels drop. I have found it useful to try to break down the names of the processes to remember the action of each process in glucose regulation, so I hope that helps.

When looking at the endocrine pancreas, there are different cell types that interact to regulate glucose. The ones we focus on most are beta cells which release insulin and alpha cells that release glucose. There are also delta cells that release somatostatin, which inhibit both alpha and beta cells. Alpha, beta and delta cells all exist in close proximity to each other in the endocrine pancreas, which allows for paracrine signalling. We learned in the communication principles unit that paracrine signalling means signalling to nearby cells without the need for a hormone or neurotransmitter.

I think of insulin as the builder, because when blood glucose levels are high, it will take glucose out of the blood and move it to tissues for storage and utilization of glucose. I think of glucagon as the breaker, because when blood glucose levels are low, it will break down stored glucose and release it into the blood because tissues and organs require a certain level of blood glucose to function.

A difficult concept to understand is that glucagon activates beta cells to stimulate the release of insulin. You make think that this is odd, since they have opposing actions. Glucagon frees glucose from storage, and then stimulates insulin so that insulin can absorb glucose into the tissues that need it. There’s a really good example in the textbook talking about a marathon runner that should explain this concept for you.

You may also be confused that alpha cells, which release glucagon, stimulate the release of somatostatin. We know that somatostatin inhibits both glucagon and insulin release, so that doesn’t seem to make much sense. An important concept we need to remember is that not all inputs are equal. Glucagon stimulates the inhibitory delta cells, but it has a much larger effect on outside tissues when it needs to do its job which is to release glucose into the blood. So delta cells wouldn’t be stimulated enough to not allow an increase in blood glucose levels when it’s necessary.
Okay now we can talk about our last subunit for this podcast- Sex Hormones.

Starting in males, we’re looking at androgenic hormones which are the hormones that give males their male characteristics, like adams apples, facial hair, etc.. Specifically in this course we focus on testosterone and its role during the sexually mature periods of a males life.

We’ll start with the form of seminiferous tubules. They are made up of a single layer of adjacent sertoli cells, and the sperm develops between two sertoli cells. Sertoli cells are also known as nurse cells which makes sense because this is where sperm cells are developing, maturing and growing so these cells are kind of nursing the sperm cells to life. Beside these cells there are peritubular cells and leydig cells which are nearby, and both play a role in sperm development through paracrine control.

When we’re looking at paracrine control, we are looking at leydig cells which begin the control. They feed testosterone (our star hormone) directly to sertoli cells and to peritubular cells. By feeding I mean they secrete them and they then act on the receiving cell, but I look at it as feeding or sending the hormones. Peritubular cells then send activating proteins to the sertoli cell. Remember that it’s not the hormones from leydig or peritubular cells that are acting on the sperm, they are simply acting on the sertoli cells which will secrete their own factors to act on the sperm or germ cells.

There also has to be feedback going back to the leydig cell so it knows how much testosterone to secrete. Estradiol and Activin send negative feedback to the sertoli cells. What do we know about negative feedback, it acts to counteract what’s happening, so it will turn the leydig cell off, no more testosterone will be secreted. From inhibin and other activating proteins, positive feedback is received, which, from what we know about positive feedback, means testosterone will continue to be secreted.

You probably noticed in this scenario that activin is being used as an inhibitor and inhibin is being used as an activating protein. This is reversed when we look at central control, activin will activate and inhibin inhibits. I remember this by remembering that central control is coming from the brain, meaning it’s logical (‘cause its the brain), and therefore it makes sense that inhibin inhibits. Then just know it’s the exact opposite when looking at paracrine control.

Now we’ll look at that central control. The cerebral cortex is going to control the overall process. It will send signals to the Hypothalamus which sends Gonadotropin Releasing Hormone(GnRH) to the anterior pituitary. The anterior pituitary sends out our key hormones, Luteinizing Hormone (LH) Follicle stimulating hormone (FSH). LH acts on Leydig cells (so Luteinizing and Leydig, L and L) and FSH acts on sertoli cells. When you’re practicing this later, consider the effects these two hormones have on the Leydig cells and the Sertoli cells and walk yourself through the whole process of secretion like we just did, starting at the cerebral cortex and working your way down to the germ cells.

We’ll talk about feedback again here because it can be confusing. The hypothalamus and the anterior pituitary are receiving negative feedback from testosterone. The cerebral cortex is receiving feedback from here as well- not negative or positive feedback, just feedback in general, like an update. The sertoli cells are also sending out feedback. Here we have inhibin and activin and, although they are now carrying their appropriate feedback again, inhibin is sending feedback to the leydig cells, while activin is sending positive feedback to the anterior pituitary. Follistatin is following the path of activin, sending negative feedback from the sertoli cells to the anterior pituitary.

I find in this particular unit, there was a bit of memory to be done. One strategy I like to use is to create mnemonics to remember specific orders of events. So for example when you’re trying to remember the path of sperm during ejaculation, from the seminiferous tubules, to the epididymus tubule, through the vas deferens, ejaculating duct, through the penis and out, take the first letter of each word in that order and create a sentence to go along with it. So S, E, V, E, P, O Smart Eager Vegetarians Eat Pickles Often. I stole that from a website for mnemonics but you can make it your own and make them as ridiculous and memorable as possible. I recommend doing this for the development of sperm as well as looking at strange letters in each of the stages, like the z in spermatozoon.

Alright now the females. So as we all know, the female system is pretty complicated. And there’s tons of charts and diagrams to understand it all but since we can’t really use those in the podcast, we’re going to try to talk you through some of the phases, what’s happening, what they’re doing and why, and let you work out some of the other smaller details from there.

A lot more than you would probably expect is actually similar to the hormone regulation of the male reproductive system. The central control for example starts out the same in both males and females, starting with the cerebral cortex, hypothalamus, GnRH, and the anterior pituitary, which also releases LH and FSH. LH acts on the Thecal cells (which are functionally similar to Leydig cells) and some Granulosa as well, and FSH acts on Granulosa cells (which are similar to Sertoli cells). Thecal cells release progesterone and both of these release estrogen which provides positive feedback back to the granulosa and thecal cells, and a variety of other factors that provide negative feedback to the hypothalamus, and anterior pituitary. Activin is providing positive feedback here.

So that’s kind of a VERY general outline of the system, we will discuss some of the changes throughout the three phases of the menstrual cycle, but I suggest looking further into some of the other details we missed such as the role of testosterone, aromatase at the level of the granulosa cells, and growth factors.

The first phase in the menstrual cycle is the follicular phase. This is the phase where the follicle is growing. The oocyte, or egg, is within the follicle, which is made up of thecal and granulosa cells. As the follicle grows, these cells release more estrogen, but they also produce more membrane receptors for estrogen, so they will receive more positive feedback from estrogen and ultimately create even more receptors. There are also more FSH and LH receptors here which come in to play in the next phase. The follicular phase ends when we’ve seen this increase or spike in estrogen for two days…

… in a row. Then ovulation begins. This is when the follicle is ruptured or broken and the oocyte is available for fertilization. This is the phase where the broken down follicle composed of thecal and granulosa cells transform into the corpus luteum, which is an endocrine organ that releases progesterone and is responsible for maintaining the endometrium. The main thing that happens in this phase is that for some unknown reason, all of those factors that are sending positive feedback to the hypothalamus and the anterior pituitary switch and become positive feedback. This means that they are being told to release more FSH and LH. So there’s a huge increase or spike in LH and FSH overall. Because there’s no explanation for that switch you just need to know when and where it happens. The LH spike is what causes the actual ovulation, which is where the oocyte waits for 24 hours for fertilization.

After those 24 hours, we have the luteal phase. Due to the degradation of the follicle, there was a very significant decrease in estrogen. The feedback that all turned positive in the last step returns to negative, and the FSH and LH levels therefore return to normal (hopefully you can follow the feedback back and tell me why that’s happening). Then either one of two things happen. Fertilization or not.

If fertilization occurs, the oocyte starts to secrete its own hormones so it can implant into the uterine wall, maintain its environment and suppress the immune system to protect it. If it is not fertilized, the corpus luteum breaks down. And because that released so much progesterone when it was intact, progesterone levels will decrease again. Then the cycle will repeat.

Okay that’s the end of our third podcast. Thanks so much for listening. Next we’ll be recording our final podcast, the Gastrointestinal Tract, so hope you tune in for that as well. Bye