all this is Dr. Moving saying from drbean.com. Welcome to one more show. So, I hope that the network is doing better today. If not, then I will have to rewire the ethernet cable, and I may have to do that over the weekend. Remember, for tomorrow, we will have Dr. Darrell Demelo speak with us tomorrow at 9:30 a.m. Pacific time instead of tomorrow evening. So, with these two, let's start our discussion. We'll continue with the androgens or male hormones. So, let me give you a summary of the androgens first, the summary of the talk today, and then we'll go in the detail. Let's see if I can do a good job at just presenting that summary in 30 seconds. The control of the androgen hormone release. Number one, keep in mind that five percent of all the androgen hormones. There are many hormones that collectively are called androgens. Five percent of them are released by suprarenal glands. Ninety-five percent are by testis. So, testosterone, ninety-five percent of that is

out of all androgens, testosterone is 95% effective and that is produced by testis. The primary control for all of these androgens, either from the suprarenal gland or from the testis, is from the hypothalamus with the pituitary and then the releasing hormones that go to these glands. So, in the case of sex hormones, male sex hormone especially, there is an effect of the emotional state as well. And from that, that means the higher centers, the executive functions of the person, the personality of the person is also influenced by the hormones, and the personality can influence the hormones. Similarly, a man's, because we're talking about androgen, a man's exposure to the sexual content itself can also affect the production of the hormones. There was a study done in which they exposed younger animals to sexual content, and they saw that they started developing or secreting androgens early on. So, this is the basic discussion today. What I will be doing is I'm gonna go over

What are the effects in the hypothalamus, then the pituitary, then what happens in the suprarenal, and then what happens in the testes, and then at the end of the discussion, I'll discuss some foods as well that can impact androgen production. So, let's start. So, once again, quick summary. Summary is that the hypothalamus releases CRH or corticotropic releasing hormones. These hormones go to the pituitary, which is another gland attached just under the hypothalamus, and I believe it is pronounced as pituitary. So, give me a chance to pronounce the way I am. Then, the pituitary has an anterior part and a posterior part. The anterior part releases ACTH, adrenocorticotropic hormone. This hormone acts on the suprarenal glands, which are the glands above the kidneys, and then it affects the secretion of androgens over there. That's only five percent. Ninety-five percent of this all is that the hypothalamus releases gonadotropin releasing hormones. Hypothalamus, you

would see, would release releasing hormones. Those releasing hormones then work on the pituitary and cause further action. So once the gonadotropin-releasing hormones are released from the hypothalamus, they act on the pituitary, and the pituitary, in response, would produce follicle-stimulating hormone or FSH and LH. FSH in men helps with spermatogenesis, and luteinizing hormone or LH is the primary hormone that helps produce testosterone from the testis. This is the 95% of the production of androgens. And here is a quick structure as we see the diagrams. This up here is the hypothalamus in the brain, above the brain stem in the central part of the brain. With hypothalamus is pituitary, and pituitary has two parts: anterior pituitary and posterior pituitary, and we'll talk more in detail. And then the effect is on the surface. That is one. The second effect is here, and once again, there is behavior of a person. We are talking men.

Then that affects the hypothalamus, and I'll go in detail for this as well. The hypothalamus releases gonadotropin-releasing hormone that then affects the pituitary, which then releases luteinizing hormone or follicle-stimulating hormone. Those then go and act on the testes, and in the testes, there are cells called Leydig cells and Sertoli cells. Leydig cells, under the influence of luteinizing hormone, produce testosterone. Sertoli cells, under the influence of follicle-stimulating hormone plus testosterone that is produced by the Leydig cells, will then in turn produce sperms or help produce sperm and support sperm and so on. So, this is the summary of all of it. We are done with the summary. If you just wanted to know this much, we have here cool. Now I'm going to go into the details. So, first of all, if we are trying to understand how are androgens produced, why are they produced, so of course, we know that they are produced in women and in men, very tiny quantity in women for the masculinizing hormone.

or the male sex hormones, more quantity in men. And so, what is the main control? The control is bilateral with personality. That is the first part. This is what they say, you know, it's all in the head. So, the personality part or behavioral part is affected by the hormones, and behavior can affect the release of the heartburn. Then, the hypothalamus receives almost all inputs from our sensory systems. So, for example, if you are, or if a person is excited or depressed, the hypothalamus receives that input to say this person at this time is happy or depressed. If there is a feeling of pain, that pain, as our brain senses the pain, a portion of that pain stimulus or signal is also sent to the hypothalamus to say we are feeling pain. Even olfaction, the smell, it goes to the amygdala, but there is a part of olfaction that is sent to the hypothalamus as well. The hypothalamus is also connected with the limbic system too, so emotional parts are also related to the hypothalamus.

hypothalamus is also connected with our anterior part of the brain or frontal lobe, which is our executive part, which is a personality part, and that also has a bilateral exchange with the hypothalamus. So, first thing here, personality. Then the second thing is the hypothalamus. Personality includes our external behavior and observation and environment as well. So, when we are sitting somewhere, standing, we are present somewhere, our personality is a lot of input, not only from our internal environment but from our external environment, and then our learnings, and then our behaviors. The hypothalamus is interested in our internal environment, so as much as external environment and personality influences it, all internal environment is influencing the hypothalamus as well. Because of that, the hypothalamus is then able to help control the body's environment by sending various executive orders to various glands. It is the superior executive branch to manage our hormones and internal systems. In addition to various sensory stimuli, our composition of the blood, that means the amount of water in the

blood or dilution of the blood was morality of the blood nutrients in the blood. How much is the glucose present? How much salt is present? How much potassium is present? And so on. All those things, water content, nutrients, other hormones, they also affect hypothalamus. So, hypothalamus at all time is fully engaged and knows external and internal state. Now, what happens next? Once the hypothalamus knows about our internal environment, let's just focus on the internal side. There are two ways hypothalamus reacts or functions. One way is hypothalamus functions through the anterior pituitary, and my apologies for the pronunciation for pituitary. This is what I know how to do it. I'll continue to improve, but this is the interior pituitary is what hypothalamus works in one case. In the other case, hypothalamus also works with the posterior pituitary. Now, it is interesting that posterior part of the pituitary or the posterior pituitary is developed from neuronal tissue, hence the connection of hypothalamus.

with the posterior pituitary is neuronal in nature. So, neurons in the hypothalamus, various parts of the hypothalamus, they send their axons that end in the posterior pituitary and release their chemical substances there and influence the action of the posterior pituitary. Today, we are not concerned with the posterior pituitary, so this is all I would talk about for that topic. We would stay more thorough with the anterior one now. Anterior pituitary, interestingly, does not develop from neuronal tissue. It actually develops from the oropharyngeal tissue, the epithelial tissue, the surface. When we are developing in our mothers, the area inside the mouth is actually an open area. It's a surface of our body, just like skin is a surface, and there are the cells. There are epithelial cells. Skin or surface cells are called epithelial cells. Some of those cells produce something called Rathke's pouch. That pouch becomes a small purse-like thing and that ascends and connects with the pituitary or under the hypothalamus.

and that makes the interior pituitary. This is why the anterior pituitary is epithelial in nature. Number one, number two, the hypothalamus connects with that not through neuronal tissues but instead through blood. So, the command from the hypothalamus to the anterior pituitary goes via blood. The commands from the hypothalamus to the posterior pituitary go through the neuronal tissue because the posterior pituitary is part of the neuronal tissue. That's a very interesting thing. So, the healthcare professionals and students here, we know that there is a hypothalamic-hypophyseal portal system. What does that mean? What is a portal system? A portal system is something where a connection between two places, two points, a connection is made through the blood system, but the connection is made in a way that there are capillaries in the beginning, then there are some blood vessels, and then there are sinuses at the end, or you can say broken tissue, broken branches of the blood vessels. They collect, they start from there, they

collect together to make trunk, then they break up into branches as well. This is called a portal system. We have a portal system in our git as well. So, hypothalamus, thalamus has a portal system. Now, here is a very interesting thing. How does it work? When hypothalamus wants to give an order to the anterior pituitary, what it does is it has neurons in various parts of it that will make the releasing or inhibitory hormones that need to go to anterior pituitary. So, there are neurons that are going to make it. However, because hypothalamus cannot directly connect with interior pituitary, there is a blood-brain barrier involved. Nervous tissue does not connect with non-nervous tissue easily. So, what happens is these neurons, if you see, see here, I'm going to zoom in. These neurons in the hypothalamus, they will make releasing hormones, and they would spill them in a place in the pituitary which is called median eminence. Median eminence. So, this is a pituitary.

stack stack is just a little a branch of the tissue or and then above the stack there is this part that is called median eminence median eminence is where the nervous system cells from hypothalamus release chemical substances. It's a beautiful mechanism. Those chemicals are then picked up by blood system. These capillaries over here are making the portal system so they take those chemicals then they become blood vessels a couple of branches. They go all the way through anterior pituitary over there. They divide in sinuses again and they bring those chemicals to the interior pituitary. This is how hypothalamus sends controls just downstairs one step below and that is either a releasing hormone or an inhibitory hormone. So now let's talk about what are those hormones those releasing or inhibiting inhibitory hormones. So once again we started with personalities effect then we started with hypothalamus as the main executive of controlling our internal environment and especially the endocrine systems behavior. Now that executive is sending chemical orders mostly releasing hormones.

to anterior pituitary. So, what are those hormones? So, if you see here, this side is hypothalamus. For example, hypothalamus sends thyroid-releasing hormone or TRH. As a result of that, anterior pituitary would listen to that and say, Okay, I'm gonna create thyroid-stimulating hormone. Then, thyroid-stimulating hormone would go to thyroid and say, Hey, thyroid, you need to make some more thyroid and release it. And thyroid would say, Okay, boss, I listen to you, and I'm gonna make some thyroid. So, three steps: hypothalamus and releasing hormone, pituitary, anterior pituitary listened to that and said, Okay, fine, I'll make releasing hormones or stimulating hormones. Then, those are sent down to the actual gland, and the gland would do its function. A couple of interesting things here: number one, this is really important and interesting. Number one, the growth hormone. When hypothalamus tells pituitary to release growth hormone, pituitary does not send the order to another gland. Instead, pituitary itself produces the

growth hormone, for example, in case of the thyroid. The hypothalamus would send an order to the pituitary to say, Please order the thyroid to function. The pituitary would then send an order to the thyroid to say, Hey, you function, and then the thyroid would function. In the case of growth hormone, that does not happen. The hypothalamus sends a message to the pituitary, and the pituitary itself acts as a gland to release growth hormone, or the hypothalamus can ask the pituitary to not release growth hormone, and the pituitary would not. So, in one case, the pituitary is acting as a gland itself. Although they're all glands, they're all releasing hormones. Another interesting thing is the prolactin in women. The milk letting or expression of milk from the breast by default is set in a way that the breast would always make and express milk. Then, it is the higher centers, hypothalamus and pituitary's job, to keep the milk expression suppressed. So, that means normally when a woman is not making milk, it is because the higher centers are

suppressing it actively, and when milk is needed, when there is a baby and there is an expression of milk that is needed, or when there is stimulation of nipples and the milk is needed, then the higher center stops suppressing the lower centers, and milk expression starts. This becomes a problem as well when many times in motor vehicle accidents, when there is a whiplash, when somebody's head comes to rest after they're going fast, or when they have a whiplash, when something hits them from behind, let's say the car, and their head goes in a jerky movement, that can cause this stack, this stack of the pituitary can break. When that breaks, and sometimes there are tumors of the pituitary, there is inflammation of the pituitary, there can be many reasons, but motor vehicle accidents is a very interesting common problem that a woman could come to a doctor and say, I had an accident two or three weeks ago, and now I continue to have milk expressed or colostrum expressed from my breasts.

and the problem is that as there is damage to the pituitary control from the hypothalamus because of the stack becoming broken. The hypothalamus does not stop the pituitary to stop the breast from expressing milk, and the result is breast start expressing milk. So, these are two interesting deviations in this process. Otherwise, the normal process is hypothalamus would send a releasing order to pituitary, which is just below it. In response to that, the pituitary would say, Fine, I'll make a hormone, which is then going to go and act on a gland and ask that gland to work now. Which two hormones we want to keep in mind here? Number one, gonadotropin-releasing hormone, because in men, that is the one that eventually would cause luteinizing hormone to come out from the pituitary. And luteinizing hormone is the one that would act on the related cells in the testes to produce testosterone. So, this is the most important access. If today's lecture, you forget everything.

and just want to remember one thing: that the hypothalamus produces GnRH (gonadotropin-releasing hormone) that causes the pituitary to produce luteinizing hormone (LH) and follicle-stimulating hormone (FSH). LH acts on the testes; we're talking about men here. It would act on testicular Leydig cells, which will then produce testosterone. That's it. If you just wanted to have one sentence for this lecture, that's it. That's the sentence. The other hormone to keep in mind today is this one: corticotropic-releasing hormone. That would cause corticotropic-releasing hormone from the hypothalamus to cause anterior pituitary release of adrenocorticotropic hormone, which would then cause suprarenal glands to produce androgens. So, androgens are being produced by the suprarenal glands and testes. Okay, continuing here, we have two kidneys. We're talking about suprarenal glands now. We have two kidneys on the top of the kidneys, the suprarenal glands, one of the glands.

look more like a semi-lunar shape. Imagine that the kidneys are wearing a hat, and one of them is wearing that little classy fancy semi-lunar hat, and the other one's hat is an old-style pyramidal hat. The suprarenal glands are about 4 grams in size. If you take a suprarenal gland and you look at the structure of it, like many other glands, it has a cortex or the outer part and a medulla or the inner part. You can call it a seed of the gland; it's not a seed bud central part. In case of suprarenal glands, the medulla is 20 in the center. This is the gland. The medulla is the part that helps with the sympathetic nervous system. This is what produces epinephrine and norepinephrine. And if I connect that to the natural killer cells, production of epinephrine will cause reduced function of natural killer cells and reduce production of natural killer cells outside of the medulla. So here, this blue one is

modula outside of medulla is cortex. Cortex in suprarenal gland is divided into three layers, and when we were in medical school, we used to remember them by saying, the deeper you go, the sweeter it becomes. And the reason is that the outermost layer, the one that I made in yellow over here, this layer is called zona glomerulosa. That is because of the cellular appearance in there, and it is the function of this layer of the cells over here is to produce mineralocorticoids. Mineralocorticoids, as the name is minerals, their function is to work with sodium, potassium, and minerals, so they are salty, right? So, our sodium balance, potassium balance is helped by aldosterone. Water balance is helped by aldosterone, which is a potent hormone coming from this layer, so that is the salty part. If you go one layer deeper, that is zona fasciculata. Zona fasciculata releases glucocorticoids. Glucocorticoids are, of course, responsible with the glucose.

metabolism or homeostasis in addition to insulin. So, insulin is the one, and then these are the ones too, so a little more sweet, and then more deeper in the cortex. This red part, the cells here are called zona reticularis, and they are the ones that produce androgens. So, that is for the men, that is a sex hormone production. Again, I'll repeat it, only five percent of all the androgens are produced here. So, suprarenals are not the main player in producing steroid hormones. Ninety-five percent of the testosterone or androgen that is testosterone comes from testis. Now, what are the hormones very quickly? Mineralocorticoid, main hormone is aldosterone. There are other two glucocorticoids, cortisol is the main hormone here, androgens from here, b hydro epi androstene, then androstenedione, then some estrogen, some glucocorticoid as well. All of these layers can produce the other layers' hormones a little bit, but they have their own primary function.

the medulla here produces the great cholamines or sympathetic chemicals. Now testosterone, so going to the 95 side, the testosterone side. So testis have multiple cells in them. One important cell, interstitial cell. Interstitial cell means the cells that are just making up the tissue of the testes. They are called Leydig cells, leading cells. Under the influence of the luteinizing hormone, make testosterone. Now please remember for all androgens, it is important that cholesterol be present. Cholesterol is important to make androgen hormones or steroid hormones. All androgen hormones are steroid hormones, or we can, we may use acetyl-CoA as well to make these. So that means cholesterol has an important role to produce testosterone. And so there are many studies that try to produce the association of less cholesterol. Would that cause less testosterone or more testosterone from exogenous use? For example, if somebody has less testosterone produced as men age, their production of testosterone reduces. That means their libido, their sex, their muscle mass, their strength.

that starts reducing, and there could be management by giving exogenous testosterone. So, there have been many studies to try to connect that. Will that cause a reduction in cholesterol or not? So, there is no clear evidence there. But just remember this much that cholesterol is necessary, first step for the production of steroid hormones. So, we cannot just be all the time upset with cholesterol. Now, once testosterone is produced, we did this discussion yesterday, the physiological and pharmacological effects of testosterone, and why am I doing this whole series. Eventually, what I want to do is that when we look at pro-androgen drugs or agonists, or when we look at anti-androgen drugs, we can understand the mechanisms behind this whole thing. So, we can say, Okay, now we have an androgen receptor blocker. We understand how would it work. You don't even need me to say it because you can look at these lectures, and then you know how androgens work. And if I say the receptor is blocked, then you can actually say what are the functions of it.

that is the point of doing these discussions. So back here when testosterone is produced, it is very rapidly used. It is supposed to be used within 30 minutes to a few hours. If we do not use it, if our cells do not use it, then testosterone is very rapidly eliminated by the liver. This is why a continuous supply of testosterone is needed. It is not that some amount is released and that is just sitting in the body forever. So it is rapidly degraded if not used. So what is the use? A major use of testosterone is in the prostate gland, and that is where the problem occurs as well. Because we discussed this yesterday, in the prostate, testosterone will be converted to dihydrotestosterone, and the function over there would actually cause this prostate gland to continue to grow. In addition to doing the contribution to semen and prostate, it does other functions too. For example, closing the urethra at the time of ejaculation, so ejaculation does not go back towards the bladder, and so on. But here what we are interested in is the

use of testosterone. So, testosterone is, of course, used in other body tissues as well. It is also used in the prostate. If testosterone is not picked up by these tissues, then the liver picks it up. And you know that with every blood circulation, our blood passes through the liver. And so, when it passes through the liver and the liver notices steroid hormone to be present, what it will do is it will degrade that. It would break it down. And how would it break it down? It would convert that into androstenedione and dihydroepiandrostenedione. Then it would conjugate that with gluconic acid. That's a normal function of the liver. It conjugates various substances, makes them water-soluble, throws them in urine or throws them in feces. That is a normal behavior of the liver. So, it does that conjugation. Now, the molecule is modified. It is ready to be eliminated. And it can be thrown out either through the bile and GIT route, fecal route, or through urine. So, that is how testosterone is very quickly removed if not used.

and now the final part. Generally, of course, it is important for us to have correct amounts of cholesterol available to make these hormones. It is also important for us to have the correct functioning structures available to make these hormones. A boy before puberty does not have functional Leydig cells, so even when there can be an order to make testosterone, they just do not have the factories to make it. And then after puberty, they have the tissue that would make it in the testis. In addition to cholesterol, in addition to working correct liver, correct testis, hypothalamus, pituitary, the fish which have vitamin D or foods that have zinc, they increase or they help produce more testosterone. When we were young, we were not very wise at that time, or um, not wise even now, but anyways, when we were young, maybe 14, 15, our mother used to say don't eat fish, it will make you warm. So now I understand that fish can actually cause men to produce more testosterone, and that can increase their libido. So sometimes men, when they eat

fish they can have is a change in libido. So, tuna, salmon, sardines, they have vitamin D. Then shellfish, crabs, lobsters, they have zinc. Beef has zinc as well, and beef has vitamin D as well. So, some of these foods can actually help produce more testosterone, and they could have an effect which is due to testosterone. So, this is the discussion again, the point of, and again, fortified milk can be taken, yogurt can be taken, cereals can be taken, vitamin D itself can be taken. And once again, the point of these discussions is to create an overall picture of how androgens work so that when we start talking about drugs that modulate them, then we are clear that why are these drugs doing what they do. So, this is the discussion for today. Thank you very much. Please like, subscribe, and share. If somebody commented on the funny glasses, so um, if you want to just help, you know, free, you can just like it, and that is sufficient help. In addition to that, if you would like to support this work.

there are three links in the description. One is to be a patron, another one is to buy me a coffee, and another one is to use PayPal to support us. And final comment for today, YouTube just before I was going to go live. I received that little update from YouTube, which said content removed, removed content. So my talk with Dr. Pier, Dr. Pier Corey, Ivermectin, Let's Help and the Pandemic, they have removed it for medical misinformation, and that has given me a warning as well. So things are becoming as hot as they can be. Looks like some people have eaten fish. So with this, I would see you in a few minutes for a chit chat. Now please remember tomorrow's talk with Dr. Daryl Demello is 9:30 a.m. Pacific time. Tomorrow we will not have a talk in the evening, we'll just have one talk in the morning, and I'm gonna try to keep my chit chat today shorter so that I can be ready for tomorrow. So with this, thank you very much, and I'll see you in

Androgens - What Controls Androgen Release? (Lecture 2)

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