welcome to the channel where medical topics are made easy in this video we're going to walk through the thyroid hormone synthesis pathway step by step a lot of these steps involve hormones or enzymes that are used to diagnose and treat thyroid conditions so knowing these steps will be helpful by the end of the video you'll know everything in the chart we're going to come back to the chart at the end so make sure to watch the entire video all of the steps along with the chart can be found in the lecture notes and study guide on our website linked down below i highly recommend checking out the lecture notes because they easily walk you through step by step everything we're going to talk about in this video all of the videos come with lecture notes and study guides so make sure to subscribe to the channel to not miss out on those there are three main structures involved in thyroid hormone regulation and synthesis they include the hypothalamus anterior pituitary gland and thyroid gland the three structures communicate and work together to produce and regulate thyroid hormone together they're called the hypothalamic pituitary thyroid axis or hpt axis for short the hpt axis is a self-regulatory circuit that balances thyroid hormone levels in the blood and maintains thyroid homeostasis in the body the pathway begins with the hypothalamus followed by the anterior pituitary gland and ends with the thyroid gland the easy way to remember the order of the three structures involved is to go in alphabetical order we have the h for hypothalamus the p for pituitary gland and the t for thyroid gland let's take a closer look at what's going on in each structure starting with the hypothalamus and pituitary gland here you can see we have zoomed in on the hypothalamus and the pituitary gland the hypothalamus is located deep in the brain below the thalamus the pituitary gland is located below the hypothalamus and it's the anterior pituitary gland that'll be important in this video let's start with the hypothalamus there are neurons located in the hypothalamus that have the ability to secrete hormones onto the anterior pituitary gland one of these groups of neurons is called the paraventricular nucleus the paraventricular nucleus secretes a hormone called thyrotropin-releasing hormone or trh this trh release from the hypothalamus is the first main step in our pathway trh will then travel to the anterior pituitary gland through the hypophyseal portal system which are the blood vessels connecting the hypothalamus and the anterior pituitary gland trh will then stimulate cells in the anterior pituitary gland called thyrotropes when the thyrotropes are stimulated by trh they will release another important hormone called thyroid stimulating hormone or tsh tsh released from the anterior pituitary gland is the second main step of our pathway once tsh is released from the anterior pituitary gland it then enters the bloodstream where it travels to another gland located in the neck this gland is called the thyroid gland which is a butterfly shaped structure located at the base of the anterior neck tsh will stimulate the thyroid gland to produce thyroid hormone before we talk about how thyroid hormone is actually synthesized in the thyroid gland let's go back to our original diagram quick and recap everything so far so we said there are three main structures involved in our pathway they include the hypothalamus anterior pituitary gland and thyroid gland the pathway starts with the hypothalamus the hypothalamus releases a hormone called thyrotropin-releasing hormone or trh trh stimulates the anterior pituitary gland to release another hormone called thyroid stimulating hormone or tsh tsh is released from the anterior pituitary gland into the bloodstream tsh circulates in the blood and binds to the thyroid gland this stimulates the thyroid gland to synthesize thyroid hormone thyroid hormone is then released from the thyroid gland into the bloodstream where it acts on many different tissues and organs in the body we're going to see that the main thyroid hormones are triiodothyronine which is t3 and thyroxine which is t4 one more trick to help you remember trh and tsh because it can be easy to mix them up or forget which one comes first you can remember these by going in alphabetical order as well use the r and trh and the s and tsh r comes before s which will help you remember the releasing hormone or trh comes first followed by the stimulating hormone or tsh now that we understand the hypothalamus and anterior pituitary gland let's take a closer look at how thyroid hormone is synthesized in the thyroid gland here you can see we have zoomed in on the thyroid gland the thyroid gland is made up of follicles which are the structural and functional units of the thyroid the follicles are lined by follicular cells which are also known as thyrocytes and the lumen or center of the follicle is filled with a substance called the colloid the thyroid gland is very vascular and filled with blood vessels the tsh that is released from the anterior pituitary gland will travel through the bloodstream and bind to the thyroid follicular cells this will stimulate the thyroid gland to produce thyroid hormone let's now take a closer look at how thyroid hormone is synthesized within the follicles here you can see we have zoomed in on a follicle and we're looking at a blood vessel in red with a follicular cell in brown above it and above that we have the lumen or colloid let's go step by step on how thyroid hormone is produced within the thyroid gland first we said the tsh released from the anterior pituitary gland circulates in the bloodstream tsh will then bind to tsh receptors on the follicular cells of the thyroid once tsh binds to tsh receptors this will stimulate or enhance the production of an important protein made by the follicular cells this protein is called thyroglobulin thyroglobulin is then released into the colloid so the colloid is very rich in thyroglobulin and we're going to see shortly that thyroglobulin is the precursor for thyroid hormone however there is one more ingredient we need from the blood to make thyroid hormone and that's iodide try not to confuse iodide and iodine because we're going to be talking about both we mainly get iodine from our diet and then it gets absorbed into the bloodstream as iodide tsh will not only enhance thyroglobulin production but it also stimulates the uptake of iodide from the blood into the follicular cell the concentration of iodide is greater in the follicular cells than the blood so iodide can't move by itself into the cell because it would be moving against its concentration gradient so iodide gets help from sodium and uses a sodium iodide symporter to get into the cell once iodide is in the follicular cell it will enter the colloid through a transporter called pendrin now that iodide is inside the lumen of the follicle the thyroid is picky and it wants iodine not iodide so it uses an enzyme called thyroid peroxidase or tpo to convert iodide into iodine this process is known as iodide oxidation because we are losing electrons to form iodine now we have our two ingredients to make thyroid hormone we have thyroglobulin and we have iodine now it's time to combine these two ingredients as we mentioned before thyroglobulin is a protein and we know proteins are made of amino acids thyroglobulin contains tyrosine amino acids the thyroid will again use the enzyme thyroid peroxidase to place iodine onto the tyrosine this process is called organification or iodination of thyroglobulin we know from our medical terminology video that the prefix mono means one and di means two so if one iodine is placed on tyrosine then it becomes mono iototyrosine or mit if two iodine are placed on tyrosine then it becomes diiodotyrosine or dit the mit and dit molecules then get combined to make t3 and t4 which are the main thyroid hormones let's look at how this works if we combine one dit which has two iodine with one mit which has one iodine then we will have two plus one which equals three iodine this will give us t3 also known as triiodothyronine if we combine two dits which each have two iodine then we will have two plus two which equals four iodine this will give us t4 also known as thyroxine or tetraiodothyronine the process of combining mit and dit molecules to form t3 and t4 is known as coupling and guess what enzyme it uses again it uses thyroid peroxidase this makes it really easy to remember because we're using the same enzyme for all these steps we don't have to remember a bunch of different enzymes so we can see thyroid peroxidase has three important roles first it's involved in oxidation where we turn iodide into iodine second it's involved in iodination where we added iodine to thyroglobulin specifically the tyrosine amino acids third it's involved in coupling the dits and mits to form t3 and t4 which are the main thyroid hormones and the cool thing is tsh will also increase the activity of thyroid peroxidase so we can see how this is all tying together so now our thyroglobulin has t3 and t4 in it which will enter back into the follicular cell through a process called endocytosis from there we have to cut the t3 and t4 out of the thyroglobulin and we do that using a proteolytic enzyme called protease t3 and t4 now enter the bloodstream to act on target tissues and organs the majority of t3 and t4 travel through the blood bound to a protein called thyroxine binding globulin or tbg now you can see how thyroid hormone is synthesized i know this was a lot of information so remember there's a great step-by-step explanation in our lecture notes of everything we just talked about it's linked down below so make sure to check that out it will help bring everything together if you need to review this more i also put together this summary to help make it easier for you it summarizes all the main steps of thyroid hormone synthesis that we talked about this chart can also be found in the lecture notes and study guide linked down below those lecture notes will walk you through each of these steps we're also going to see in future videos when we talk about thyroid conditions how things like trh tsh t3 t4 thyroglobulin and thyroid peroxidase are all important players in diagnosing and treating those conditions hopefully this gave you a better understanding of thyroid hormone synthesis remember you can find the step-by-step explanations of everything we talked about in the lecture notes and study guide on our website linked down below if you found the video useful please hit that like button and leave a comment make sure to subscribe so you don't miss out on future videos notes and study guides thanks for watching and hope you check out future videos