Nonclassical Actions of Vitamin D

Introduction:

Vitamin D is a fat-soluble vitamin as well as a hormone that our body produces. Vitamin D is mostly produced in the skin from sunlight, and some amount of it is absorbed from food. About ten percent of the total vitamin D is absorbed from the diet. The primary function of vitamin D is to increase the intestinal absorption of calcium, magnesium, phosphate, etc. Studies suggest that vitamin D also helps in controlling infections and reducing inflammation along with fighting cancer cells.

Vitamin D is a group of compounds, and the most important compounds in this group are vitamin D3 (cholecalciferol) and vitamin D2 (ergocalciferol). Vitamin D plays a crucial role in calcium homeostasis and metabolism. Since vitamin D can be synthesized by most mammals from sunlight, it is not necessarily a hormone. In fact, it can be classified as a hormone. Cholecalciferol is converted into calcifediol which is further hydroxylated by the kidneys and some immune cells to form calcitriol. It is the biologically active form of vitamin D, and this calcitriol circulates in the blood in the form of a hormone.

How Is Vitamin D Produced?

Apart from being absorbed from a healthy diet, vitamin D is photochemically produced in the skin when it is exposed to sunlight. The skin consists of two primary layers; the dermis (inner layer) and the epidermis (outer and thinner layer). Vitamin D is produced in the keratin-producing cells (keratinocytes) present in the epidermis. The keratinocytes present in the stratum basale and stratum spinosum of the epidermis produce vitamin D.

What Is the Mechanism of Action of Vitamin D?

Whether ingested as a supplement or photosynthesized in the skin, vitamin D is carried to the liver via blood, where it is converted into the prohormone calcifediol. This circulating calcifediol is then hydroxylated into calcitriol (the biologically active form of vitamin D) by the kidneys.

What Are the Nonclassical Actions of Vitamin D?

Apart from the general functions associated with calcium absorption and metabolism, there are several other functions carried out by vitamin D. The nonclassical actions of vitamin D can be broadly classified into three groups:

1. Regulation of hormone secretion.

2. Regulation of immune function.

3. Regulation of cellular proliferation and differentiation.

There may be more nonclassical actions of vitamin D apart from the ones mentioned above.

1. Regulation of Hormone Secretion: Vitamin D has the ability to regulate hormone secretion, which plays a key role in maintaining normal bone mineral homeostasis. The hormones affected by vitamin D are:

• Parathyroid Hormone: Vitamin D inhibits the production and secretion of parathyroid hormone. Vitamin D also prevents the proliferation of parathyroid glands. The thyroid gland contains a negative vitamin D response element (a type of DNA sequence) through which it exerts suppression. The active form of vitamin D represses the parathyroid gene transcription and blocks parathyroid principal cell hyperplasia (enlargement due to an increased rate of reproduction of cells). Therefore, when the vitamin D concentration is low in the body, calcium absorption in the intestine also diminishes, leading to low calcium levels in the blood. As a result, the parathyroid gland becomes overactive and produces more parathyroid hormone. Therefore, vitamin D is an integral tool for treating secondary hyperparathyroidism in patients with renal diseases.

• Insulin: Several studies have shown a link between vitamin D deficiency and insulin resistance. Vitamin D plays a vital role in developing insulin resistance and the pathogenesis of type 2 diabetes mellitus. Vitamin D affects insulin sensitivity and beta-cell functions. Vitamin D reduces insulin resistance due to its effect on calcium and phosphorus metabolism and through the regulation of insulin receptor genes. A number of studies have shown that vitamin D supplements have increased insulin sensitivity.

• Fibroblast Growth Factor-23 (FGF23): Fibroblast growth factor 23 is primarily produced in the bones by the osteoblasts and osteocytes (bone-forming and bone-resorbing cells). FGF23 also plays a crucial role in vitamin D metabolism; it inhibits vitamin D production by the kidneys, thus forming a feedback loop. This feedback loop helps maintain a balance in these hormones' levels.

2. Regulation of Immune Function: The active form of vitamin D to regulate the body's immunological response has been discovered. Vitamin D is essential in regulating innate and adaptive immunity, influencing multiple clinical conditions. Innate immunity is the body's defense response with which an individual is born. In contrast, adaptive immunity results from exposure to a disease organism that triggers the immune system to form antibodies against that disease.

3. Regulation of Proliferation and Differentiation: Vitamin D affects cellular proliferation by modulating various processes, including apoptosis (physiologic and programmed death of a cell in an organism), cell cycle progression, and differentiation in a cell-specific manner. The anti-proliferative and pro- differentiation actions of vitamin D are also beneficial in preventing cancer to an extent. Studies have reported that vitamin D has been found to have several actions that might slow or prevent cancer cell growth. To prevent cancer, vitamin D promotes cell differentiation, decreases the growth of cancer cells, stimulates apoptosis, and reduces tumor blood vessel formation.

What Are the Other Functions of Vitamin D?

There are a few other nonclassical actions of vitamin D, including:

• Xenobiotic (substance that is synthetic or foreign to the body) detoxification.

• Oxidative stress reduction.

• Neuroprotective functions.

• Antimicrobial defense.

• Immunoregulation.

• Cardiovascular benefits.

Conclusion:

Vitamin D is a vitamin as well as a hormone that our body produces. Vitamin D is photosynthesized in the stratum basale and stratum spinosum of the epidermis layer of the skin when it is exposed to sunlight. And some amount of vitamin D is also ingested from food as a part of a healthy diet. The primary function of vitamin D has always been associated with its skeletal function. It has been known to be involved in the absorption of calcium, magnesium, and phosphate. Vitamin D helps in regulating the serum calcium and phosphate levels; it also helps in bone growth and reorganization through its actions on osteoblast (bone-forming cells) and osteocytes (cells responsible for bone resorption as well as bone-deposition). However, in recent times nonclassical or novel actions of vitamin D have been reported. These nonclassical actions of the vitamin include regulation of hormone secretion, regulation of both innate and active immunity, and regulation of cellular proliferation and differentiation.