 Dr. O'Hare, everybody, Dr. O'Hare here. Hopefully, you remember from our first chapter together that the body is designed to maintain homeostasis, the maintenance of a stable internal environment. And most of the time when it does, so it uses negative feedback. For positive feedback, we talked about a couple of examples, blood clotting and labor and delivery. So, there are some hormones that rely on positive feedback. So, I'm going to just quickly talk about that, oxytocin, which is the primary hormone that leads to the ejection of the baby, I guess you'd say, during labor and delivery is actually, so it's going to, the initiation of labor and delivery is going to trigger more and more oxytocin being released and more muscle contraction, which is going to push the baby onto the, onto the cervix, which is going to stimulate more oxytocin release, which is going to push the baby harder. That's an example of a positive feedback system driven by hormones. But other than that, almost every other hormone we're going to talk about relies on negative feedback. So, let's talk about that. Negative feedback means that there's a change right in the body. There's a change to a concentration of a hormone. The response will be to negate that change, to keep it from getting out of, out of control. So, I'll give you, I'll, we'll, we'll walk through this example here with thyroid hormones and then I'll also give another one with your sex hormones. Let's start here with number one. We'll start with low, so you have low thyroid hormone levels where hypothalamus is going to sense that and it's going to release what's called a regulatory hormone, thyrotropin releasing hormone that's going to tell the pituitary gland to release thyroid stimulating hormone, which is going to tell the thyroid gland to release thyroid hormones, which are called T4 and T3. We'll cover them in more, more detail later. Now you have a bunch of thyroid hormones doing their job. Well, the, the higher levels of T3 and T4, your thyroid hormones is going to tell the hypothalamus, okay, we're good. We don't, we don't need any more thyroid hormone right now. So the thigh, the hypothalamus will stop producing thyrotropin releasing hormone, which will tell the pituitary gland to stop producing thyroid hormone. You see, so the end result is that you keep your thyroid hormones pre-level. Now if it starts to dip again, then you're going to see it go up. If it goes too high, you're going to see it shut down. That's negative feedback trying to maintain a stable amount of thyroid hormone. Now you notice here in the middle, if there was already too much thyroid hormone, then these, the system would shut off and allow that thyroid hormone to be used up. So that's a really good example of how negative feedback works. So we can use this if we're going to be diagnosing thyroid conditions. So if someone has hypothyroidism, for example, you'd want to know, is the problem in the pituitary gland or is it in the thyroid gland? Well, you can sort of tell by looking at the lab results. If someone has low T3 and T4 levels, you know that they have hypothyroidism. They don't, they're not producing enough thyroid hormone. But the question is, why not? So the typical person that is hypothyroid will have low T3 and T4 levels, but they will have high TSH levels, thyroid stimulating hormone. This means that their hypothalamus is working fine because it's telling the pituitary gland to make thyroid stimulating hormone. It's telling you that the pituitary gland is working fine because it's churning out excess thyroid stimulating hormone. It's begging the thyroid gland to start making thyroid hormone. So we know in this case, the problem is the thyroid gland. It could be the person is iodine deficient, so they can't make thyroid hormone or it could be an inflammatory condition. The most common cause of hypothyroidism in the United States is an autoimmune condition called Hashimoto's thyroiditis. So now, but what if someone comes in? They have low thyroid hormone levels and they have low TSH levels. Now we know the pituitary gland is not doing its job. Now it would take further imaging and work to figure out why not. But so the thyroid gland is sitting there not making thyroid hormone, but there's nothing wrong with a thyroid gland, or at least we can't tell because the pituitary gland isn't telling it to make thyroid hormone. So you see how looking at the lab results, you can actually see where in this negative feedback system something is wrong, something's broken. On the opposite side, if someone has hyperthyroidism, their T4 and T3 levels will be elevated. They will have too much thyroid hormone. Their TSH level should be really, really low because their pituitary gland should be saying, wait, there's already like too much thyroid hormone. I'm not gonna keep making more. So that's an example of negative feedback. So Ruby's having a dream, my dog there. Another example would be your sex hormone. So maybe you've heard that when let's say we'll just use men, when men use anabolic steroids, that their testicles will shrink and that there will be testicular atrophy. Well, that is true because normally the hypothalamus would be looking for sex hormone levels and if the sex hormone levels were low, then it would tell the pituitary gland to produce what are called the gonadotropins, follicle stimulating hormone and luteinizing hormone, which would tell the gonads, in this case the testicles, luteinizing hormone would say make testosterone. So which the testicles would do and a man's testosterone would go up. That's what would happen if someone has too little. If someone has too much testosterone then the system's gonna shut off and say we have to use the testosterone that we have. There's no reason to keep making more. Well, if someone is injecting themselves with anabolic steroids, their testosterone levels are gonna be through the roof. So this system's gonna basically shut off and stay shut off because the hypothalamus can tell there's too much testosterone. So the testicles would atrophy to some extent because they're not producing testosterone, they're not being used. This is also why though, that long-term use of anabolic steroids can lead to sterility, make a man's sterile. Because if you shut off this system, you're also shutting off the system that leads to the maturation of sperm. So sperm count could drop and there are drugs that can be used to try to counteract that but I'm just giving you another example. So this is how negative feedback is used to control almost all of your hormone levels plus that one example I gave you of positive feedback with oxytocin. Okay, I hope this helps. Have a wonderful day. Be blessed.