previtamin-d(3) and 7-dehydrocholesterol

Vitamin D is generally accepted in its importance on the regulation of calcium homeostasis and bone metabolism. Moreover, further health effects due to vitamin D are under discussion. In its effect, vitamin D is more like a hormone. In the classic view, a vitamin is an essential nutrient, which cannot be synthesized independently in the body. Besides nutrition, vitamin D will be produced in the body itself. The skin contains the provitamin D3 7-dehydrocholesterol, a precursor of vitamin D. Provitamin D3 will be photoconverted to previtamin D3 by UVB radiation that penetrates the skin superficially. In this way, the vitamin D metabolism will be started independent of the nutrition. In everyday life, this photosynthesis will be carried out due to the solar UVB radiation penetrating the uncovered skin. In the same spectral waveband range of UVB radiation, which causes the beneficial health effect of starting the vitamin D metabolism, the UVB radiation causes simultaneously acute and chronic harmful health effects as UV erythema (sunburn), skin aging and skin cancer. There is no vitamin D production in the skin without simultaneous DNA damage in the skin. Against this background, risks and benefits have to be balanced carefully.

Topics: Cholecalciferol; Dehydrocholesterols; Humans; Metabolic Networks and Pathways; Skin; Skin Aging; Skin Neoplasms; Sunburn; Ultraviolet Rays; Vitamin D

Vitamin D is the sunshine vitamin for good reason. During exposure to sunlight, the UV B photons enter the skin and photolyze 7-dehydrocholesterol to previtamin D3 which in turn is isomerized by the body's temperature to vitamin D3. Most humans have depended on sun for their vitamin D requirement. Skin pigment, sunscreen use, aging, time of day, season and latitude dramatically affect previtamin 13 synthesis. Vitamin D deficiency was thought to have been conquered, but it is now recognized that more than 50% of the world's population is at risk for vitamin D deficiency. This deficiency is in part due to the inadequate fortification of foods with vitamin D and the misconception that a healthy diet contains an adequate amount of vitamin D. Vitamin D deficiency causes growth retardation and rickets in children and will precipitate and exacerbate osteopenia, osteoporosis and increase risk of fracture in adults. The vitamin D deficiency has been associated pandemic with other serious consequences including increased risk of common cancers, autoimmune diseases, infectious diseases and cardiovascular disease. There needs to be a renewed appreciation of the beneficial effect of moderate sunlight for providing all humans with their vitamin D requirement for health.

Topics: Aging; Bone Diseases, Metabolic; Cholecalciferol; Dehydrocholesterols; Humans; Osteoporosis; Photolysis; Rickets; Skin; Skin Neoplasms; Skin Pigmentation; Sunlight; Sunscreening Agents; Ultraviolet Rays; Vitamin D; Vitamin D Deficiency

The universally recognised action spectrum for the UV-induced conversion of 7-dehydrocholesterol to previtamin D(3) in human skin was published in 1982, and indicates a maximum at about 297 nm with essentially no production above 315 nm. This work represents a milestone in research on vitamin D, but limitations in the original data should be recognised. Various findings have arisen in recent years which cast doubts on the accuracy of the action spectrum and its application for spectral weighting in calculations of effective UV doses. In conclusion, the construction of an entirely new computational model to predict previtamin D levels is recommended.

Topics: Cholecalciferol; Dehydrocholesterols; Humans; Skin; Ultraviolet Rays

Topics: Adult; Aged; Animals; Calcifediol; Calcitriol; Child; Cholecalciferol; Dehydrocholesterols; Dihydroxycholecalciferols; Ergocalciferols; Female; Humans; Hydroxycholecalciferols; Infant, Newborn; Liver; Nutritional Requirements; Pregnancy; Skin; Species Specificity; Ultraviolet Rays; Vitamin D; Vitamin D Deficiency

Topics: Cholecalciferol; Dehydrocholesterols; Dose-Response Relationship, Radiation; Humans; Skin; Ultraviolet Rays

Skin is in the site of previtamin D3 and vitamin D3 synthesis and their isomerization in response to ultraviolet irradiation. At present, little is known about the function of the photoisomers of previtamin D3 and the vitamin D3 in skin cells. In this study we investigated the antiproliferative activity of the major photoisomers and their metabolites in the cultured human keratinocytes by determining their influence on 3H-thymidine incorporation into DNA. Our results demonstrated at both 10(-8) and 10(-6) M in a dose-dependent manner. Lumisterol, tachysterol3, 5,6-trans-vitamin D3, and 25-hydroxy-5,6-trans-vitamin D3 only induced significant inhibition at 10(-6) M. 25-Hydroxytachysterol3 was approximately 10- to 100-fold more active than tachysterol3. 7-Dehydrocholesterol was not active even at 10(-6) M. The dissociation constants of vitamin D receptor (VDR) for 25-hydroxytachysterol3, 25-hydroxy-5,6-trans-vitamin D3, and 5,6-trans-vitamin D3 were 22, 58, and 560 nM, respectively. The dissociation constants for 7-dehydrocholesterol, tachysterol, and lumisterol were greater than 20 microM. In conclusion, vitamin D3, its photoisomers and the photoisomers of previtamin D3 have antiproliferative activity in cultured human keratinocytes. However, the antiproliferative activity did not correlate with their binding affinity for VDR. The results suggest that some of the photoproducts may be metabolized to their 25-hydroxylated and 1 alpha,25-dihydroxylated counterparts before acting on VDR. Alternatively, a different receptor may recognize these photoproducts or another mechanism may be involved in modulating the antiproliferative activity of the photoisomers examined.

Topics: Calcitriol; Cells, Cultured; Cholecalciferol; Dehydrocholesterols; DNA; Dose-Response Relationship, Drug; Ergosterol; Humans; Isomerism; Keratinocytes; Photobiology; Receptors, Calcitriol; Sunlight; Thymidine; Ultraviolet Rays

The photoproduction of vitamin D in the skin was essential for the evolutionary development of terrestrial vertebrates. During exposure to sunlight, previtamin D3 formed in the skin is isomerized to vitamin D3 (calciol) by a temperature-dependent process. Since early land vertebrates were poikilothermic, the relatively slow conversion of previtamin D3 to vitamin D3 at ambient temperature put them at serious risk for developing vitamin D deficiency, thus leading to a poorly mineralized skeleton that could have ultimately halted further evolutionary development of vertebrates on land. We evaluated the rate of isomerization of previtamin D3 to vitamin D3 in the skin of iguanas and found the isomerization rate was enhanced by 1100% and 1700% at 25 degrees C and 5 degrees C, respectively. It is likely that the membrane entrapment of previtamin D3 in its s-cis,s-cis conformation is responsible for the markedly enhanced conversion of previtamin D3 to vitamin D3. The membrane-enhanced production of vitamin D3 ensures the critical supply of vitamin D3 to poikilothermic animals such as iguanas.

Topics: Animals; Biological Evolution; Body Temperature Regulation; Cholecalciferol; Dehydrocholesterols; Hot Temperature; Humans; Iguanas; In Vitro Techniques; Isomerism; Rana temporaria; Skin

The cutaneous synthesis of vitamin D3 and the subsequent translocation of vitamin D3 into the circulation are two key steps in the vitamin D endocrine system. To study the kinetic aspects of cutaneous synthesis and translocation of vitamin D3, both in vitro and in vivo chicken models have been developed. To assess the capacity of chicken skin to generate vitamin D3, the concentrations of 7-dehydrocholesterol (7-DHC) in different skin areas were determined. It was found that the highest concentration of 7-DHC was in the leg skin (3524 +/- 937 ng cm-2), which was about 30 times greater than that in the back (120 +/- 62 ng cm-2). Whole body exposure of chickens to UV-B radiation (0.5 J cm-2) resulted in the production of previtamin D3 (preD3) in the skin of the legs and feet (43 +/- 7 and 54 +/- 17 ng cm-2, respectively), whereas no preD3 was detected in the back skin. In vitro, at 40 C, the forward (k1) and reverse (k2) rate constants of the preD3<-->vitamin D3 reaction in the leg skin were greatly increased compared to those in n-hexane (k1, 0.367 vs. 0.0369 h-1; k2, 0.042 vs. 0.0059 h-1). In vivo, the determined rate constants k1, k2, and k3 for the consecutive reactions preD3<-->vitamin D3-->vitamin D3 were 0.257, 0.034, and 0.114 h-1, respectively. To evaluate the circulating concentration of vitamin D3 in response to UV-B radiation, chicken legs were irradiated. The time course revealed a 4-fold increase in the circulating concentration of vitamin D3, with a peak about 30 h postradiation. No appreciable amount of preD3 could be detected in the circulation in the early hours after UV-B radiation, suggesting the existence of a process responsible for the specific translocation of vitamin D3 from the skin into the circulation.

Topics: Animals; Biological Transport; Chickens; Cholecalciferol; Dehydrocholesterols; Extremities; Female; Kinetics; Models, Biological; Skin; Ultraviolet Rays

The preparation of milligram quantities of three vitamin D3 isomers, previtamin D3, lumisterol3 and tachysterol3, were carried out in a laboratory scale first by irradiating 7-dehydrocholesterol in a phototherapy chamber equipped with UVB lamps, followed by using a two-step high performance liquid chromatography (HPLC) with a semi-preparative normal phase column and an analytical reverse-phase column. The final products obtained were identified by UV spectrophotometry and HPLC. According to the detection limits for the three isomers, no contamination with any other isomers was detected in the previtamin D3, lumisterol3 and tachysterol3 preparations, except that a very small amount of vitamin D3, constituting no more than 0.25% of the product, was found in previtamin D3 preparation.

Topics: Cholecalciferol; Chromatography, High Pressure Liquid; Dehydrocholesterols; Ergosterol; Isomerism

Exposure to sunlight continues to play a major role in providing adequate vitamin D nutrition for most of the population of the world, including those who live in countries that practice fortification of dairy, margarine, and cereal products with vitamin D. During exposure to sunlight, the high-energy UV photons (290-315 nm) penetrate the epidermis and photolyze 7-dehydrocholesterol (provitamin D3) to previtamin D3. Once formed, previtamin D3 undergoes a thermally induced isomerization to vitamin D3 that takes 2-3 days to reach completion. Melanin effectively competes with provitamin D3 for the UV radiation that enters the epidermis and limits its photolysis to previtamin D3. However, this is not the major factor that prevents excess production of vitamin D in the skin of people who are constantly exposed to sunlight. During the initial exposure to sunlight, provitamin D3 is efficiently converted to previtamin D3. However, because previtamin D3 is photolabile, continued exposure to sunlight causes the isomerization of previtamin D3, principally to lumisterol. Thus, no more than 10-20% of the initial provitamin D3 concentrations ultimately end up as previtamin D3. Aging, sunscreens, seasonal changes, time of day, and latitude also significantly affect the cutaneous production of this vitamin-hormone.

Topics: Aging; Cholecalciferol; Dehydrocholesterols; History, 17th Century; History, 18th Century; History, 19th Century; History, 20th Century; Humans; Life Style; Melanins; Rickets; Skin; Sunlight; Sunscreening Agents; Ultraviolet Rays; Vitamin D

With delineation of the photochemical events occurring in the skin after ultraviolet exposure, there has been increased interest in the skin's role in the vitamin D-3-endocrine system. We provide here in vitro conditions for the generation of both labelled (from [3H]acetate) and unlabelled vitamin D-3 in cultures of human keratinocytes and fibroblasts. Sterol precursors and photoproducts in irradiated and non-irradiated cultures are identified by co-chromatography, ultraviolet absorbance spectra, thermal conversion characteristics of previtamin D-3 and mass spectrometry. Because the conversion of 7-dehydrocholesterol to cholesterol is more efficient in vitro than in vivo, the specific delta 7 inhibitor, AY-9944, was added in non-toxic doses to modulate 7-dehydrocholesterol content. Both cell types were equally capable of generating photoproducts, depending on the amount of 7-dehydrocholesterol present. The 290 +/- 5 and 295 nm filters were much more efficient than the 305 nm filter for generating previtamin D-3 and vitamin D-3 in fibroblasts. In contrast, the 305 nm filter was as efficient as the 290 +/- 5 and 295 nm filters in keratinocytes, where it yielded previtamin D-3, with much less lumisterol and tachysterol than appeared with the shorter-wavelength filters. The amount of lumisterol and tachysterol versus previtamin D-3 formed in both cell types was dependent on the total energy applied, with lower energies (less then 1 J/cm2) favoring previtamin D-3 over the other photoproducts. The use of cultured cells provides a system whereby the regulation of vitamin D-3 synthesis by extracutaneous factors can be studied in a homogeneous setting.

Topics: Aldehyde Oxidoreductases; Cells, Cultured; Cholecalciferol; Cholesterol; Cyclohexanes; Dehydrocholesterols; Ergosterol; Fibroblasts; Glycolaldehyde Dehydrogenase; Humans; Microscopy, Electron; Skin; Spectrum Analysis; trans-1,4-Bis(2-chlorobenzaminomethyl)cyclohexane Dihydrochloride

Topics: Calcitriol; Cholecalciferol; Dehydrocholesterols; Ergosterol; Humans; Isomerism; Skin; Skin Pigmentation; Stereoisomerism; Sunlight; Temperature; Ultraviolet Therapy; Vitamin D; Vitamin D Deficiency

The photosynthesis of previtamin D3 from 7-dehydrocholesterol in human skin was determined after exposure to narrow-band radiation or simulated solar radiation. The optimum wavelengths for the production of previtamin D3 were determined to be between 295 and 300 nanometers. When human skin was exposed to 295-nanometer radiation, up to 65 percent of the original 7-dehydrocholesterol content was converted to previtamin D3. In comparison, when adjacent skin was exposed to simulated solar radiation, the maximum formation of previtamin D3 was about 20 percent. Major differences in the formation of lumisterol3, and tachysterol3 from previtamin D3 were also observed. It is concluded that the spectral character of natural sunlight has a profound effect on the photochemistry of 7-dehydrocholesterol in human skin.

Topics: Cholecalciferol; Dehydrocholesterols; Ergosterol; Humans; In Vitro Techniques; Isomerism; Photochemistry; Skin; Spectrum Analysis; Structure-Activity Relationship; Ultraviolet Rays

When human skin was exposed to simulated solar ultraviolet radiation, epidermal 7-dehydrocholesterol was converted to previtamin D3. During prolonged exposure to simulated solar ultraviolet radiation, the synthesis of previtamin D3 reached a plateau at about 10 to 15 percent of the original 7-dehydrocholesterol content, and previtamin D3 was photoisomerized to two biologically inert isomers, lumisterol3 and tachysterol3. Increases either in skin melanin concentration or in latitude necessitated increases in the exposure time to simulated solar ultraviolet radiation required to maximize the formation, but not the total content, of previtamin D3. In order of importance, the significant determinants limiting the cutaneous production of previtamin D3 are (i) photochemical regulation, (ii) pigmentation, and (iii) latitude.

Topics: Animals; Calcium; Cholecalciferol; Dehydrocholesterols; Dose-Response Relationship, Radiation; Environment; Ergosterol; Humans; In Vitro Techniques; Photochemistry; Rats; Skin; Skin Pigmentation; Sunlight; Ultraviolet Rays

Topics: Animals; Calcitriol; Cholecalciferol; Cholestadienols; Dehydrocholesterols; Hot Temperature; Molecular Conformation; Photochemistry; Rats; Skin; Skin Physiological Phenomena; Skin Temperature; Ultraviolet Rays; Vitamin D