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Vitamin D is a group of fat-soluble prohormones, the two major forms of which are vitamin D2 (or ergocalciferol) and vitamin D3 (or cholecalciferol). Vitamin D obtained from sun exposure, food, and supplements, is biologically inert and must undergo two hydroxylation reactions to be activated in the body. Calcitriol (1,25-Dihydroxycholecalciferol) is the active form of vitamin D found in the body. The term vitamin D also refers to these metabolites and other analogues of these substances. Calcium regulation in the human body. The role of vitamin D is shown in orange.
Calcitriol plays an important role in the maintenance of several organ systems. However, its major role is to increase the flow of calcium into the bloodstream, by promoting absorption of calcium and phosphorus from food in the intestines, and reabsorption of calcium in the kidneys; enabling normal mineralization of bone and preventing hypocalcemic tetany. It is also necessary for bone growth and bone remodeling by osteoblasts and osteoclasts.
Without sufficient vitamin D, bones can become thin, brittle, or misshapen. Deficiency can arise from inadequate intake coupled with inadequate sunlight exposure; disorders that limit its absorption; conditions that impair conversion of vitamin D into active metabolites, such as liver or kidney disorders; or, rarely, by a number of hereditary disorders. Vitamin D deficiency results in impaired bone mineralization and leads to bone softening diseases, rickets in children and osteomalacia in adults, and possibly contributes to osteoporosis.
Vitamin D plays a number of other roles in human health including inhibition of calcitonin release from the thyroid gland. Calcitonin acts directly on osteoclasts, resulting in inhibition of bone resorption and cartilage degradation. Vitamin D can also inhibit parathyroid hormone secretion from the parathyroid gland, modulate neuromuscular and immune function and reduce inflammation.
Production in the skin
The epidermal strata of the skin. Production is greatest in the stratum basale (colored red in the illustration) and stratum spinosum (colored orange).
The skin consists of two primary layers: the inner layer called the dermis, composed largely of connective tissue, and the outer, thinner epidermis. The epidermis consists of five strata; from outer to inner they are: the stratum corneum, stratum lucidum, stratum granulosum, stratum spinosum, and stratum basale.
Vitamin D3 is produced photochemically in the skin from 7-dehydrocholesterol; 7-dehydrocholesterol is produced in relatively large quantities in the skin of most vertebrate animals, including humans. The few exceptions are some bat species, mole rats, cats, and dogs, which produce little vitamin D. In most animals the highest concentrations of 7-dehydrocholesterol are found in the epidermal layer of skin, specifically in the stratum basale and stratum spinosum. The production of pre-vitamin D3 is therefore greatest in these two layers, whereas production in the other layers is less.
Synthesis in the skin involves UVB radiation, which effectively penetrates only the epidermal layers of skin. While 7-dehydrocholesterol absorbs UV light at wavelengths between 270–300 nm, optimal synthesis occurs in a narrow band of UVB spectra between 295-300 nm. Peak isomerization is found at 297 nm. This narrow segment is sometimes referred to as D-UV. The two most important factors that govern the generation of pre-vitamin D3 are the quantity (intensity) and quality (appropriate wavelength) of the UVB irradiation reaching the 7-dehydrocholesterol deep in the stratum basale and stratum spinosum.
A critical determinant of vitamin D3 production in the skin is the presence and concentration of melanin. Melanin functions as a light filter in the skin, and therefore the concentration of melanin in the skin is related to the ability of UVB light to penetrate the epidermal strata and reach the 7-dehydrocholesterol-containing stratum basale and stratum spinosum. Under normal circumstances, ample quantities of 7-dehydrocholesterol (about 25-50 µg/cm² of skin) are available in the stratum spinosum and stratum basale of the skin to meet the body's vitamin D requirements, and melanin content does not alter the amount of vitamin D that can be produced. Thus, individuals with higher skin melanin content will simply require more time in sunlight to produce the same amount of vitamin D as individuals with lower melanin content. The amount of time an individual requires to produce a given amount of vitamin D may also depend upon the person's distance from the equator and on the season of the year.
In some animals, the presence of fur or feathers blocks the UV rays from reaching the skin. In birds and fur-bearing mammals, vitamin D is generated from the oily secretions of the skin deposited onto the fur and obtained orally during grooming.
In 1923, Harry Goldblatt and Katherine Soames established that when 7-dehydrocholesterol (a precursor of vitamin D in the skin) is irradiated with light, a form of a fat-soluble vitamin is produced. Alfred Fabian Hess and Mildred Weinstock further substantiated that "[sun]light equals vitamin D". Adolf Windaus, at the University of Göttingen in Germany, received the Nobel Prize in Chemistry in 1928, for his work on the constitution of sterols and their connection with vitamins. In 1930s, he clarified further the chemical structures of the vitamins D.
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