PTH up-regulates 25-hydroxyvitamin D3 1-alpha-hydroxylase, the enzyme responsible for 1-alpha hydroxylation of 25-hydroxy vitamin D, converting vitamin D to its active form (1,25-dihydroxy vitamin D). This activated form of vitamin D increases the absorption of calcium (as Ca2+ ions) by the intestine via calbindin. PTH was one of the first hormones to be shown to use the G-protein adenylyl cyclase second messenger system. Regulation of serum phosphate
PTH reduces the reabsorption of phosphate from the proximal tubule of the kidney, which means more phosphate is excreted through the urine. However, PTH enhances the uptake of phosphate from the intestine and bones into the blood. In the bone, slightly more calcium than phosphate is released from the breakdown of bone. In the intestines, absorption of both calcium and phosphate is mediated by an increase in activated vitamin D. The absorption of phosphate is not as dependent on vitamin D as is that of calcium. The end result of PTH release is a small net drop in the serum concentration of phosphate. Vitamin D synthesis
PTH upregulates the activity of 1-α-hydroxylase enzyme, which converts 25-hydroxycholecalciferol, the major circulating form of inactive vitamin D, into 1,25-dihydroxycholecalciferol, the active form of vitamin D, in the kidney. Interactive pathway map
Regulation of PTH secretion
Secretion of parathyroid hormone is determined chiefly by serum ionized calcium concentration through negative feedback. Parathyroid cells express calcium-sensing receptors on the cell surface. PTH is secreted when [Ca2+] is decreased (calcitonin is secreted when serum calcium levels are elevated).
Avascular necrosis (AVN), also called osteonecrosis or bone infarction, is death of bone tissue due to interruption of the blood supply. Early on, there may be no symptoms. Gradually joint pain may develop which may limit the ability to move. Complications may include collapse of the bone or nearby joint surface.Risk factors include bone fractures, joint dislocations, alcoholism, and the use of high-dose steroids. The condition may also occur without any clear reason. The most commonly affected bone is the femur. Other relatively common sites include the upper arm bone, knee, shoulder, and ankle. Diagnosis is typically by medical imaging such as X-ray, CT scan, or MRI. Rarely biopsy may be used.Treatments may include medication, not walking on the affected leg, stretching, and surgery. Most of the time surgery is eventually required and may include core decompression, osteotomy, bone grafts, or joint replacement. About 15,000 cases occur per year in the United States. People 30 to 50 years old are most commonly affected. Males are more commonly affected than females. Signs and symptoms
In many cases, there is pain and discomfort in a joint which increases over time. While it can affect any bone, about half of cases show multiple sites of damage.Avascular necrosis most commonly affects the ends of long bones such as the femur. Other common sites include the humerus, knees, shoulders, ankles and the jaw. Causes
The main risk factors are bone fractures, joint dislocations, alcoholism, and the use of high-dose steroids. Other risk factors include radiation therapy, chemotherapy, and organ transplantation.