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Vitamin D: An Evolving Star

By: Peter T. Pugliese, MD
Posted: June 29, 2009, from the July 2009 issue of Skin Inc. magazine.
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The metabolically active form of vitamin D is released into circulation and binds to a carrier protein in the plasma—vitamin D binding protein (VDBP)—which transports it to various target organs. To have biological effects, the hormonally active form of vitamin D must next bind to a receptor—vitamin D receptor (VDR)—located in the nuclei of target cells. After binding to the VDR, it acts as a transcription factor that modulates the gene expressions that are involved with calcium absorption in the intestine. The vitamin D receptor belongs to the nuclear receptor superfamily of steroid/thyroid hormone receptors, which are expressed by cells in most organs, including the brain, heart, skin, gonads, prostate and breast. It is the vitamin D receptor activation in the intestine, bone, kidney and parathyroid gland cells that leads to the maintenance of calcium and phosphorus levels in the blood, with the assistance of parathyroid hormone and calcitonin, and to the maintenance of bone content.

The VDR is known to be involved in cell proliferation and differentiation. Vitamin D also affects the immune system, and VDR is expressed in several white blood cells, including monocytes and activated T and B cells.

Calcium is a tightly regulated substance. The concentration in the blood plasma must be held constantly at 10 mg/100 mL of the total calcium. Many of life’s essential functions depend on calcium being constantly available. A few of these include signal transmission in nerves, the contraction and relaxation of muscle tissue, exocrine secretion, blood-clotting, cellular adhesion and the construction of an entire skeleton. To maintain calcium at a constant level, a process called calcium homeostasis occurs, which is a very complex task that involves many hormones, some of which are unknown. Managing the calcium of plasma is the most important role of vitamin D in the endocrine system, a task it shares with the parathyroid hormone and a substance called calcitonin. See Figure 2.

The parathyroid gland is the calcium-sensing organ. A slight drop in the calcium plasma level, known as hypocalcemia, will cause the parathyroid gland to react within seconds to secrete parathyroid hormone (PTH).1 This is followed by a sequence of events that mobilizes calcium to restore the normal plasma level. The calcium receptor in the parathyroid gland is well-known and appears to act to facilitate the secretion of PTH, which has a very short lifespan in plasma, in minutes, if not seconds.2

There is a receptor for the PTH found throughout the length of the nephron of the kidney, in the osteoblasts (bone cells that lay down calcium), but not the osteoclasts (bone cells that absorb calcium) of the skeleton. In the kidney, the PTH blocks reabsorption of the phosphate, causing a loss of phosphate. Several hormonal functions of PTH relate to its role in the formation of vitamin D in the kidney. The following references will expand these facts for those who are interested.3–5