Today we will talk about the parathyroid gland. Now concerning the parathyroid gland.

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1 Today we will talk about the parathyroid gland The lecture started when one of the students asked about the difference between the cortisol and cortisone. And the doctor answer was that both are hormones but synthetic cortisol is very much stronger than cortisone. Now concerning the parathyroid gland. They are four glands located behind the thyroid gland so having more than four glands is abnormal and they might be located in some other locations in the body not only behind the thyroid. In addition to this, when the thyroid is removed surgically the parathyroid glands might be removed also. However, removing one or two glands might not be harmful but if three glands were removed then it might cause serious problems. Each gland is composed of two types of cells: 1- Chief cells 2- oxyphil cells All the parathyroid hormone (PTH) is secreted by the chief cells only. The oxyphil cells have two theories : 1) These cells play in the metabolism of the parathyroid glands 2) they may be modified or depleted chief cells that no longer secrete the PTH and this theory fits more, because

2 these cells are not found in young people histologically, and they start to appear after the age of 14 or 18. Now, when we talk about the four parathyroid glands, it reflects the importance the calcium in the body, so we are not human being without the presence of calcium the compose the skeleton mainly. The parathyroid glands start to develop at 4 weeks of gestation, but the range is too much wide; from 5 to 14 weeks. in addition to this, we said the parathyroid glands secrete the PTH which is a protein hormone. The physiological activity of this hormone resides at the first 34 amino acids, so if we removed the amino acids 35 and above, the hormone would be still functional. The PTH sometimes produces many second messengers, such as camp, diacylglycerol (for the activation of the enzymes ) and the IP3 ( inositol triphosphate) for the calcium. Sometimes, the PTH might produce all the second messengers together, depending on the place of the organ where the PTH is secreted.

3 PTH has 3 receptors: 1) binds just to the PTH 2) binds to the PTH and other proteins ( hormones) which are similar to the PTH which are called PTH similar hormone 3) binds to the PTH only or to the PTH- similar hormone only ( so it doesn t bind to both hormones together) The PTH has a short have life, which is 25 minutes, but it is essential for life because calcium is essential for life because without the calcium, tetany will occur. So PTH is secreted or stimulated by calcium ions in the plasma, also the calcium regulates the number and the growth of the parathyroid cells. Of course, the PTH is the main regulator for plasma calcium level. Magnesium is also important for the secretion of PTH but it is less potent than calcium in such role. Moreover, phosphate is also important for the stimulation of the PTH and 1,25 vitamin D derivative directly reduces the PTH secretion. PTH functions on the bone by increasing the resorbtion of calcium from the bones to rise the calcium level in the plasma. PTH also functions on the kidneys by increasing the calcium reabsorption and decrease the phosphate reabsorption, also the PTH produces 1,25 vitamin D derivative.

4 Vitamin D ( hormone D) works on the intestine to elevate the calcium absorption, so the result is normalizing plasma calcium level, and also normalizing the plasma phosphate level but during this, it increases the calcium and decreases phosphate always in order to maintain their levels at a normal range. Now, we will talk about the deficiency of PTH. What happens? 1) reduced calcium resorbtion in the bone 2) reduced calcium reabsorption from the kidneys 3) reduced production of vitamin D in the kidney and consequently, reduced calcium absorption. So as a result, the calcium level will be very low, but when it reaches 6 mg / 100 ml in plasma, tetany will occur. However, the normal range of calcium in the plasma is mg/100 ml plasma, but if plasma calcium level becomes lower than 4 mg/100 ml in the plasma, death occurs. So we can see that the border line is 5 6 mg/100 ml. Now, we will move to talk about the overactivity of PTH. What happens? 1) a lot of calcium is resorbed so this will cause softening in the bone which is a disease that is called Osteitis Fibrosa Cystica.

5 2) a lot of calcium re- absorption in the kidney and a lot of phosphate is excreted. 3) a lot of vitamin D is produced in the intestine so a lot of calcium is absorbed from there. 4) the plasma calcium level will rise above 16 mg / 100 ml in the plasma and this will cause many problem, in which the viscosity of the blood increases, and this patient will suffer from continuous thirst and polyurea (severity in urination) just like the diabetic patient but with different causes. 5) deposition of calcium in an unusual sights such as the kidney with signs of calcium toxicity. Now, we will talk about a new hormone which has a very important role and it is the major regulator for the calcium and phosphate metabolism which is hormone D or vitamin D. This hormone (vitamin) is considered as a hormone because it is produced in the body and then it is released in the blood to function with no specific gland. But this hormone is considered also as a vitamin, because we can obtain it from the food. However, vitamin D ( D2 or D3 ) and hormone D are both processed in the liver and the kidney to become 1,25 vitamin D derivative. After that they are stored in the body ( liver and adipose tissue) to be used in need.

6 Now, the main function of vitamin D is the mineralization of bones. So if the deficiency of vitamin D occurs in children, rickets occurs. Whereas in adults, osteomalcia occurs which is also called adult rickets. This 1,25 vitamin D derivative is transported to the kidney to be processed again to produce two metabolites ; very active 1,25 vitamin D derivative and the low active 24,25 vitamin D derivative; both derivatives are active but they differ in their potency, and those two derivatives circulate in the plasma bound with proteins. We obtain vitamin D3 ( cholecalciferol) and vitamin D2 ( sorry I couldn t hear its name) from the food. Both are processed in the liver to become prohormones transported into the kidneys to produce 1,25 or 24,25 or both derivatives depending on the need. Anyone of these indicates the need of hormone, therefore, vitamin D deficiency stimulates an enzyme in the kidney to produce 1,25 vitamin D derivative or calcium deficiency or phosphate deficiency or PTH deficiency. Anyone of these indicates the fact that the body does not need vitamin D too much, therefore 24,25 derivative is produced and 1,25 derivative is in excess, The phosphate is in excess, and the calcium also is in excess. All these activate the( 24 - vitamin D hydroxylase ). We can understand the potency from the half life so 1,25 half- life is 2 days followed by 25 vitamin D derivative then 24,25

7 derivative. All these circulate in the plasma bound to plasma proteins. Relations between the PTH and vitamin D in the bone : The vitamin D ( hormone D) has a similar function to the PTH in the intestine: it increases both calcium and phosphate absorption ( opposite to the PTH) in the kidney : it also increases the re- absorption of both (calcium and phosphate). So we can see when we look deeply that PTH and vitamin D work in an antagonistic way but actually they act in a synergistic way because vitamin D mainly functions on the mineralization of the new bone which is called bone remodeling, but the PTH functions over all the body parts, mainly on the calcium. As a result, they both function in a synergistic way. Done by: (عمرر بنن االخططابب ( صبيیح