Moving vitamin D around the body
Vitamin D, 25(OH)D3, and calcitriol are carried in the blood by a vitamin D-binding protein. This protein is necessary because these substances aren’t water soluble and can’t dissolve in blood. (Vitamin D dissolves in fat). Ninety-nine percent of all the different forms of vitamin D are bound to the vitamin D binding protein, and only 1 percent is free to enter cells.
The different forms of vitamin D that are bound to the vitamin D binding protein are protected from destruction by cells and excretion by the kidneys. Only the 1 percent that’s free is available to carry out the functions of active vitamin D.
The Life History of Vitamin D
Pregnancy and estrogen use are a few conditions that can result in increased production of vitamin D-binding protein. These conditions cause the body to make more active vitamin D to take up all the extra binding sites, but the amount that’s free and able to enter cells usually remains normal. Calcitriol levels more than double during pregnancy but it’s only in the third trimester that free levels of calcitriol increase above normal.
Putting vitamin D to work
The best-understood role for the calcitriol is in the control of how your body uses calcium and phosphorus to make strong bones. However, research is showing that many organs and systems in your body may also need active vitamin D. The intestine and bones rely on the kidneys to make and ship calcitriol to them. However, the other organs that need calcitriol may be able to make small amounts on their own.
Active vitamin D works by entering cells and attaching to a protein called the vitamin D receptor, located in the nucleus of cells, where the genetic material is located. This combination of calcitriol and its receptor stimulates the cell to make proteins that regulate the way the body works. For example, some of the proteins produced in response to calcitriol in the intestine help transport calcium across the intestine and into the bloodstream, greatly increasing the absorption of calcium from the diet. The vitamin D receptor is found in several cells that are critical for controlling the metabolism of calcium, phosphorus, and bone: intestinal cells, bone cells, kidney cells, and parathyroid gland cells.
Vitamin D receptors also are present in most other tissues, including the brain, heart, skin, ovary and testicle, prostate gland, and breasts, as well as the cells of the immune system, including white blood cells and other key immune cells. In fact, at least 33 different tissues contain the vitamin D receptor.
• Adipose (fat)
• Adrenal
• Bone
• Bone marrow
• Brain
• Breast
• Cartilage
• Colon (large intestine)
• Epididymis
• Hair follicle
• Kidney
• Liver
• Lung
• Lymphocytes
• Muscle, embryonic
• Muscle, heart
• Muscle, smooth
• Osteoblast (bone-forming cell)
• Ovary
• Pancreas
• Parathyroid
• Parotid
• Pituitary
• Placenta
• Prostate
• Retina
• Skin
• Small intestine
• Stomach
• Testis
• Thymus
• Thyroid
• Uterus
Vitamin D’s effects on your cells
Calcitriol has two different ways to influence cells: a genomic action, which may take hours to days to occur, and a rapid response, which can occur in minutes.
In genomic action, calcitriol binds to the vitamin D receptor and together the active vitamin D and its receptor attach to the DNA. This interaction affects the activity of more than 500 genes. Each of these genes produces a protein; some of these proteins regulate calcium and bone metabolism whereas others may help protect cells from cancer, influence insulin secretion, and affect the immune response.
The rapid responses don’t’ result from attachment of the vitamin D receptor to the genes in the nucleus. Here are three examples of rapid responses:
• White blood cells take up calcium rapidly when calcitriol is added. This action takes place when calcitriol and its receptor attach to the membrane that surrounds the cell.
• Calcitriol also protects skin cells from the damaging effects of ultraviolet irradiation. This effect may be the function of other substances produced when vitamin D forms in the skin.
• The rapid uptake of calcium from the intestine is considered to be another example of a rapid response, as is the rapid secretion of insulin in response to glucose.
These rapid responses have only been studied in cultured cells, not in the body.