The Parathyroid Gland

The Parathyroid gland There are four parathyroid glands in the human body. These glands are peasized and behind the right and left superior and inferior lobes of the thyroid It contains chief cells which synthesises, stores and secretes parathyroid hormone (PTH). The role of PTH is to regulate calcium within the body: in the ECF compartment and in the bone compartment. This hormone is sritical to life, since calcium is important in the functioning of the heart’s SA node and bundle of Hiss. Decreased extracellular calcium concentrations produce arrhythmias which can stop the heart from beating and lead to death. The parathyroid hormone is a peptide hormone, 84 amino acids long, synthesised as a pre-prohormone of 115 amino acids, cleaved to a pro-hormone of 90 amino acids and is finally produced into PTH. Next for PTH to be active, it has to be lysed by the liver where only the N-terminal is active, with the C terminal being inactive. The half life of parathyrpid hormone is less than five minutes since there are a lot of peptidases that break it down as it circulates through the blood. PTH’s receptor is a G protein coupled receptor. It signals w=either via the Gs subunit, where cAMP is produced which activates protein kinase A or the Gq subunit, which mediates a signalling pathway via phospholoapse C which activates protein kinase C which releases intracellular calcium stores. Calcium is controlled by PTH at every level, its absorption and its reabsorption in the kidney, and its regulation in the bone stores. Bone is in a constant state of turnover: bone resorption and bone formation. In fractures, for example, calcium is laid down to help healing: isteoblasts are responsible for this. Osteoclasts on the othr hand remove calcium and is responsible for resorption and pit formation. In lactose intolerant individuals, osteoporosis (resorbing of bone) starts at the age of 25. This happens because these individuals have not taken in enough calcium, and bone has not been laid down properly in these first 25 years- where bone completely matures. For bones to be healthy there should be an equal bone formation and bone resorption. Kidneys also play a role in the extracellular concentration of calcium. 98% of the filtered calcium is reabsprbed, hence a very minimal proportion of calcium is excreted. Reabsorption takes place 60-70% in the proximal convoluted tubule, which is passive and fluxed with Na+ uptake, 20% in the thick ascending limb which is also passive and follows water reabsorption and sodium and potassium reabsorption and most importantly 5-10% in the distal tubule and collectind duct, which are effected by the parathyroid gland. Increased reabsorption of calcium depends on: increased parathyroid hormone, decreased calcitonin, alkali, thiazide diuretics and lithium which is a drug given for depression and bipolar disease. Decreased reabsorption includes: excess dietry salts, excess calcium and magnesium, loop diuretics, acid and calcitonin. Active calcium reabsorption involves the calcium CHANNELS on the luminal surface which facilitate the entry of calcium, which then binds to calbindin and is taken to the basolateral

membrane. It is the pumped out of the cell by the ca2+/ATPase pump or by a Na+/Ca2+ exchanger. In order for calcium to be absorbed from the intestine, it undergoes solubilisation in the stomach acid. The greatest rate of absorption is from the duodenum and jejunum, where the pancreas secretes alkali substances. If the alkiali concentration is too much however there will be precipitation of the Ca2+ as a salt. If there is a high concentration of calcium, calcium travels passively down its concentration gradient, if however the calcium concentration is low their is active absorption of calcium. This process is aided by the parathyroid hormone: which is stimulkated at low calcium concentrations. Absorption is also aides by vitamin D and sugars(due to osmolarity changes). A decrease in absorption, is also elicited by sluable fibre and phosphates. Vitamin D is a hormone, which influences other organs to regulate their calcium metabolism. Lack of Vitamin D leads to rickets, which could be due to lack of vitamin D in the diet or a mutation in the vitamin D receptor. In the skin 7dehydrocholesterol is convertedby UVB from sunlight to vitamin D, which bunds to a vitamin D binding protein and then in the liver it enters cells since vitamin D is lipophilic, and vitamin D is hydroxylated at the 25 position. This form is inactive. It travels via systemic blood to reach the kidney via a vitamin D binding protein, here it undergoes hydroxylation at the 24 or 1 position: onl the latter is active. Not a lot of items have vitamin D, and this could be a problem for pigmented individuals travelling to less sunny area. I Eng;and, to avoid this problem they add vitamin D to milk. Problems with liver and kidney may also lead to vitamin D metabolism. Thje vitamin D receptor is intracellular since it is lipophilic.The mechanism of action is very similar to T3 and retinoic acid, where the vitamin D binding to receptor activates transcription of certain genes. Vitamin D is synthesised by sunlight, stimulated by PTH, decreased calcium concentrations in the serum and decreased phosphates. Decrease in its synthesis results from pigmentation, due to blockage by melanocyte of its formation, low PTH, high calcium and phosphate serum levels. The functions of vitamin D is to decrease PTH, increase intestinal calcium absorption, increase bone resorption, suppress 1 hydroxylate, stimulate 24 hydroxylate, increase renal reabsorption in vitamin D deficient animals. All this results to incease the calcium and phosphate concentration inthe serum. Calcitonin is a 32 amino acid formed from C cells of the thyroid glands. Its secretion is stimulated by increased calcium concentrations and gastrin. At pharmacological doses it increases renal exretion of Ca2+. Calcitonin also decreases bone resorptoion by binding to osteoclasts. A calcium sensing receptor that also binds magnesium, since their regulation often goes in parallel, is found in the parathyroid hormone, the C cells of the thyroid gland, the kidneys, the intestines, bone and the brain. It has an activating mutation: where it sense increased calcium and shits up the thyroid causing hypothyroidism and an inactivating mutation : familial hypocalciuric hypocalemia.

In the pituitary prolactin and GH are produced and may activate 1,25 vitamin D to increase bone formation. Oestrogen is also important for bone formation as is testosterone. Steroids on the other hand increase bone resorption and interferes with parathyroid hormone and vitamin D metabolism.The immune system is also involved with certain interleukins causing osteoclastogenesis. In the serum a PTH related peptide with 141 amino acids is found. The N terminal 13 aminoacids are homologous to PTH. Hence markers for the first 13 amino acids recognise both PTH and the PTH related hormone. In the embryo this molecule prevents premature ossification, it is produced in some tumours where it has PTH like effects. It also arboroses the lacteal system in the breast and maintains smooth muscle tone.