RSS-Feed abonnieren
DOI: 10.1055/s-2007-958715
© Georg Thieme Verlag KG Stuttgart · New York
Vitamins as Hormones
Publikationsverlauf
received 23. 11. 2006
accepted 28. 11. 2006
Publikationsdatum:
27. Februar 2007 (online)
![](https://www.thieme-connect.de/media/hmr/200702/lookinside/thumbnails/10.1055-s-2007-958715-1.jpg)
Abstract
Vitamins A and D are the first group of substances that have been reported to exhibit properties of skin hormones, such as organized metabolism, activation, inactivation, and elimination in specialized cells of the tissue, exertion of biological activity, and release in the circulation. Vitamin A and its two important metabolites, retinaldehyde and retinoic acids, are fat-soluble unsaturated isoprenoids necessary for growth, differentiation and maintenance of epithelial tissues, and also for reproduction. In a reversible process, vitamin A is oxidized in vivo to give retinaldehyde, which is important for vision. The dramatic effects of vitamin A analogues on embryogenesis have been studied by animal experiments; the clinical malformation pattern in humans is known. Retinoic acids are major oxidative metabolites of vitamin A and can substitute for it in vitamin A-deficient animals in growth promotion and epithelial differentiation. Natural vitamin A metabolites are vitamins, because vitamin A is not synthesized in the body and must be derived from carotenoids in the diet. On the other hand, retinoids are also hormones - with intracrine activity - because retinol is transformed in the cells into molecules that bind to and activate specific nuclear receptors, exhibit their function, and are subsequently inactivated. The mechanisms of action of natural vitamin A metabolites on human skin are based on the time- and dose-dependent influence of morphogenesis, epithelial cell proliferation and differentiation, epithelial and mesenchymal synthetic performance, immune modulation, stimulation of angiogenesis and inhibition of carcinogenesis. As drugs, vitamin A and its natural metabolites have been approved for the topical and systemic treatment of mild to moderate and severe, recalcitrant acne, photoaging and biologic skin aging, acute promyelocytic leukaemia and Kaposi's sarcoma. On the other hand, the critical importance of the skin for the human body's vitamin D endocrine system is documented by the fact that the skin is both the site of vitamin D3- and 1,25-dihydroxyvitamin D3 [1, 25(OH)2D3]-synthesis and a target organ for 1,25(OH)2D3. 1,25(OH)2D3 is not only essential for mineral homeostasis and bone integrity, but also for numerous further physiologic functions including regulation of growth and differentiation in a broad variety of normal and malignant tissues, including cells derived from prostate, breast and bone. In keratinocytes and other cell types, 1,25(OH)2D3 regulates growth and differentiation. Consequently, vitamin D analogues have been introduced for the treatment of the hyperproliferative skin disease psoriasis. Other newly detected functions of vitamin D analogues include profound effects on the immune system as well as protection against cancer and other diseases, including autoimmune and infectious diseases, in various tissues. Current investigation of the biological effects of vitamin D analogues are likely to lead to new therapeutic applications that, besides cancer prevention, may include the prevention and treatment of infectious as well as of inflammatory skin diseases. This review summarizes existing knowledge on vitamins A and D, the major vitamin-hormones of the skin.
Keywords
vitamins - vitamin A - vitamin D - hormones - retinoids - skin protection
References
- 1 Safavi K. Serum vitamin A levels in psoriasis: Results from the first national health and nutrition examination survey. Arch Dermatol. 1992; 128 1130-1131
- 2 Tang G, Russel RM. 13-cis-retinoic acid is an endogenous compound in human serum. J Lipid Res. 1990; 31 175-182
- 3 Matsuoka LY, Wortsman J, Tang G. et al . Are endogenous retinoids involved in the pathogenesis of acne?. Arch Dermatol. 1991; 127 1072-1073
- 4 Biesalski HK. Comparative assessment of the toxicology of vitamin A and retinoids in man. Toxicology. 1989; 57 117-161
- 5 Vieira AV, Schneider WJ, Vieira PM. Retinoids: Transport, metabolism, and mechanisms of action. J Endocrinol. 1995; 146 201-207
- 6 Giguère V. Retinoic acid receptors and cellular retinoid binding proteins: Complex interplay in retinoid signaling. Endocrine Rev. 1994; 15 61-79
- 7 Ross AC. Cellular metabolism and activation of retinoids: roles of cellular retinoid-binding proteins. FASEB J. 1993; 7 317-327
- 8 Zouboulis CC, Seltmann H, Sass JO, Rühl R, Plum C, Hettmannsperger U, Blume-Peytavi U, Nau H, Orfanos CE. Retinoid signaling by all-trans retinoic acid and all-trans retinoyl-β-d-glucuronide is attenuated by simultaneous exposure of human keratinocytes to retinol. J Invest Dermatol. 1999; 112 157-164
- 9 Craven NM, Griffiths CEM. Topical retinoids and cutaneous biology. Clin Exp Dermatol. 1996; 21 1-10
-
10 Mangelsdorf DJ, Umesono K, Evans RM. The retinoid receptors. In: Sporn MB, Roberts AB, Goodman DS (eds).
The retinoids. Biology, Chemistry, and medicine 3rd ed. New York: Raven Press 1994: 319-349 - 11 Tsukada M, Schröder M, Roos TC, Chandraratna RAS, Reichert U, Merk HF, Orfanos CE, Zouboulis CC. 13-cis Retinoic acid exerts its specific activity on human sebocytes through selective intracellular isomerization to all-trans retinoic acid and binding to retinoid acid receptors. J Invest Dermatol. 2000; 115 321-327
- 12 Carlberg C, Saurat JH. Vitamin D3-retinoids association: Molecular basis and clinical application. J Invest Dermatol Symp Proc. 1996; 1 82-86
- 13 Reichrath J, Mittmann M, Kamradt J, Muller SM. Expression of retinoid-X receptors (-alpha, -beta, -gamma) and retinoic acid receptors (-alpha, -beta, -gamma) in normal human skin: an immunohistological evaluation. Histochem J. 1997; 29 127-133
-
14 Siegenthaler G, Saurat J-H. Natural retinoids: metabolism and transport in human epidermal cells. In: Saurat J-H (ed.)
Retinoids: 10 years on . Basel: Karger 1991: 56-68 -
15 Doran TI, Lucas DA, Levin AA, Pacia E, Sturzenbecker L, Allenby G, Grippo JF, Shapiro SS. Biochemical and retinoid receptor activities in human sebaceous cells. In: Saurat J-H (ed).
Retinoids: 10 years on . Basel: Karger 1991: 243-253 - 16 Reichrath J, Munssinger T, Kerber A, Rochette-Egly C, Chambon P, Bahmer FA, Baum HP. In situ detection of retinoid-X receptor expression in normal and psoriatic human skin. Br J Dermatol. 1995; 133 168-175
-
17 Zouboulis CC, Orfanos CE. Retinoids. In: Millikan LE (ed).
Drug Therapy in Dermatology . New York: Marcel Dekker 2000: 171-233 - 18 Saurat J-H. Systemic retinoids - What's new?. Dermatol Clin. 1998; 16 331-340
- 19 Roos TC, Jugert FK, Merk HF, Bickers DR. Retinoid metabolism in the skin. Pharm Rev. 1998; 50 315-333
- 20 Karlsson T, Vahlquist A, Kedishvili N, Törmä H. 13-cis-Retinoic acid competitively inhibits 3 alpha-hydroxysteroid oxidation by retinol dehydrogenase RoDH-4: a mechanism for its anti-androgenic effects in sebaceous glands?. Biochem Biophys Res Commun. 2003; 303 273-278
- 21 Orfanos CE, Zouboulis CC, Almond-Roesler B, Geilen CC. Current use and future potential role of retinoids in dermatology. Drugs. 1997; 53 358-388
- 22 Rollman O, Wood EJ, Olsson MJ, Cunliffe WJ. Biosynthesis of 3,4-didehydroretinol from retinol by human skin keratinocytes in culture. Biochem J. 1993; 293 675-682
- 23 Kang S, Duell EA, Fisher GJ, Datta SC, Wang ZQ, Reddy AP, Tavakkol A, Yi JY, Griffiths CEM, Elder JT, Voorhees JJ. Application of retinol to human skin in vivo induces epidermal hyperplasia and cellular retinoid binding proteins characteristic of retinoic acid but without measurable retinoic acid levels or irritation. J Invest Dermatol. 1995; 105 549-556
- 24 Duell EA, Åström A, Griffiths CEM, Chambon P, Voorhees JJ. Human skin levels of retinoic acid and cytochrome P-450-derived 4-hydroxyretinoic acid after topical application of retinoic acid in vivo compared to concentrations required to stimulate retinoic acid receptor-mediated transcription in vitro. J Clin Invest. 1992; 90 1269-1274
- 25 Kurlandsky SB, Xiao J-H, Duell EA, Voorhees JJ, Fisher GJ. Biological activity of all-trans-retinol requires metabolic conversion to all-trans-retinoic acid and is mediated through activation of nuclear receptors in human keratinocytes. J Biol Chem. 1994; 269 32821-32827
- 26 Randolph RK, Simon M. Metabolism of all-trans-retinoic acid by cultured human epidermal keratinocytes. J Lipid Res. 1997; 38 1374-1383
- 27 Baron JM, Heise R, Blaner WS, Neis M, Joussen S, Dreuw A, Marquardt Y, Saurat JH, Merk HF, Bickers DR, Jugert FK. Retinoic acid and its 4-oxo metabolites are functionally active in human skin cells in vitro. J Invest Dermatol. 2005; 125 143-153
- 28 Kistler A. Limb bud cell cultures for estimating the teratogenic potential of compounds: Validation of the test system with retinoids. Arch Toxicol. 1987; 60 403-414
- 29 Lammer EJ, Chen DT, Hoar RM, Agnish ND, Benke PJ, Braun JT, Curry CJ, Fernhoff PM, Grix Jr AW, Lott IT. et al . Retinoic acid embryopathy. N Engl J Med. 1985; 313 837-841
- 30 Tong PS, Horowitz NN, Wheeler LA. Trans-retinoic acid enhances the growth response of epidermal keratinocytes to epidermal growth factor and transforming growth factor beta. J Invest Dermatol. 1990; 94 126-131
- 31 Zheng Z-S, Polakowska R, Johnson A, Goldsmith LA. Transcriptional control of epidermal growth factor receptor by retinoic acid. Cell Growth Differ. 1992; 3 225-232
- 32 Zouboulis CC, Korge B, Akamatsu H, Xia L, Schiller S, Gollnick H, Orfanos CE. Effects of 13-cis-retinoic acid, all-trans-retinoic acid and acitretin on the proliferation, lipid synthesis and keratin expression of cultured human sebocytes in vitro. J Invest Dermatol. 1991; 96 792-797
- 33 Zouboulis CC, Korge BP, Mischke D, Orfanos CE. Altered proliferation, synthetic activity, and differentiation of cultured human sebocytes in the absence of vitamin A and their modulation by synthetic retinoids. J Invest Dermatol. 1993; 101 628-633
- 34 Asselineau D, Darmon M. Retinoic acid provokes metaplasia of epithelium formed by adult human epidermal keratinocytes. Differentiation. 1995; 58 297-306
- 35 Asselineau D, Bernard BA, Bailly C, Darmon M. Retinoic acid improves epidermal morphogenesis. Dev Biol. 1989; 133 322-335
- 36 Saavalainen K, Pasonen-Seppanen S, Dunlop TW, Tammi R, Tammi MI, Carlberg C. The human hyaluronan synthase 2 gene is a primary retinoic acid and epidermal growth factor responding gene. J Biol Chem. 2005; 280 14636-14644
- 37 Melnik B, Kinner T, Plewig G. Influence of oral isotretinoin treatment on the composition of comedonal lipids. Implications for comedogenesis in acne vulgaris. Arch Dermatol Res. 1988; 280 97-102
- 38 Geiger J-M, Hommel L, Harms M, Saurat J-H. Oral 13-cis retinoic acid is superior to 9-cis retinoic acid in sebosuppression in human beings. J Am Acad Dermatol. 1996; 34 513-515
- 39 Shapiro SS, Hurley J, Vane FM, Doran T. Evaluation of potential therapeutic entities for the treatment of acne. In: Pharmacology of Retinoids in the Skin. Basel: Karger 1989: 104-112
-
40 Zouboulis CC, Xia L, Korge B, Gollnick H, Orfanos CE. Cultivation of human sebocytes in vitro. Cell characterization and influence of synthetic retinoids. In: Saurat J-H (ed).
Retinoids 10 years on . Basel: Karger 1991: 254-273 - 41 Zouboulis CC, Krieter A, Gollnick H, Orfanos CE. Progressive differentiation of human sebocytes in vitro is characterized by increased cell size and altered antigenic expression and is regulated by culture duration and retinoids. Exper Dermatol. 1994; 3 151-160
- 42 Nelson AM, Gilliland KL, Cong Z, Thiboutot DM. 13-cis Retinoic acid induces apoptosis and cell cycle arrest in human SEB-1 sebocytes. J Invest Dermatol. 2006; , [Epub ahead of print]
- 43 Buck J, Derguini F, Levi E, Nakanishi K, Hammerling U. Intracellular signaling by 14-hydroxy-4,14-retro-retinol. Science. 1991; 254 1654-1656
- 44 Halliday GM, Ho KK, Barnetson RS. Regulation of the skin immune system by retinoids during carcinogenesis. J Invest Dermatol. 1992; 99 83S-86S
- 45 Prabhala RH, Maxey V, Hicks MJ, Watson RR. Enhancement of the expression of activation markers on human peripheral blood mononuclear cells by in vitro culture with retinoids and carotenoids. J Leukocyte Biol. 1989; 45 249-254
- 46 Bollag W. Retinoid and interferon: A new promising combination?. B J Haematol. 1991; 79 ((Suppl 1)) 87-91
- 47 Halewy O, Arazi Y, Melamed D, Friedman A, Sklan D. Retinoic acid receptor-alpha gene expression is modulated by dietary vitamin A and by retinoic acid in chicken T lymphocytes. J Nutr. 1994; 124 2139-2146
- 48 Wozel G, Chang A, Zultak M, Czarnetzki BM, Happle R, Barth J, van de Kerkhof PC. The effect of topical retinoids on the leukotriene-B4-induced migration of polymorphonuclear leukocytes into human skin. Arch Dermatol Res. 1991; 283 158-161
- 49 Bécherel P-A, Mossalayi MD, Le Goff L, Francès C, Chosidow O, Debré P, Arock M. Mechanism of anti-inflammatory action of retinoids on keratinocytes. Lancet. 1994; 344 1570-1571
- 50 Imcke E, Ruszczak Zb, Mayer-da-Silva A, Detmar M, Orfanos CE. Cultivation of human dermal microvascular endothelial cells in vitro: Immunocytochemical and ultrastructural characterization and effect of treatment with three synthetic retinoids. Arch Dermatol Res. 1991; 283 149-157
- 51 Gollnick H, Orfanos CE. Theoretical aspects of the use of retinoids as anticancer drugs. In: Retinoids in cutaneous malignancy. Oxford: Blackwell 1991: 41-65
- 52 Layton AM, Dreno B, Gollnick HPM, Zouboulis CC. A review of the European directive for prescribing systemic isotretinoin for acne vulgaris. J Eur Acad Dermatol Venereol. 2006; 20 773-776
- 53 Jick SJ, Terris B, Jick H. First trimester topical tretinoin and congenital disorders. Lancet. 1993; 341 1181-1182
- 54 Zouboulis CC. Retinoids - Which dermatological indications will benefit in the near future?. Skin Pharmacol Appl Skin Physiol. 2001; 14 303-315
- 55 Griffiths CEM, Russman AN, Majmudar G, Singer RS, Hamilton TA, Voorhees JJ. Restoration of collagen formation in photodamaged skin by tretinoin (retinoic acid). N Engl J Med. 1993; 329 530-535
- 56 Talwar HS, Griffiths CEM, Fisher GJ, Hamilton TA, Voorhees JJ. Reduced type I and type III procollagens in photodamaged adult human skin. J Invest Dermatol. 1995; 105 285-290
- 57 Fisher GJ, Wang Z-Q, Datta SC, Varani J, Kang S, Voorhees JJ. Pathophysiology of premature skin aging induced by ultraviolet light. New Eng J Med. 1997; 337 1419-1428
- 58 Fisher GJ, Datta S, Wang Z, Li XY, Quan T, Chung JH, Kang S, Voorhees JJ. C-jun-dependent inhibition of cutaneous procollagen transcription following ultraviolet irradiation is reversed by all-trans retinoic acid. J Clin Invest. 2000; 106 663-670
- 59 Fisher GJ, Voorhees JJ. Molecular mechanisms of photoaging and its prevention by retinoic acid: Ultraviolet irradiation induces MAP kinase cascades that induce AP-1 - regulated matrix metalloproteinases that degrade human skin in vivo. J Invest Dermatol. 2003; 101 ((Suppl)) S61-S68
- 60 Papakonstantinou E, Aletras AJ, Glass E, Tsogas P, Dionyssopoulos A, Adjaye J, Fimmel S, Gouvousis P, Herwig R, Lehrach H, Zouboulis CC, Karakiulakis G. Matrix metalloproteinases of epithelial origin in facial sebum of patients with acne and their regulation by isotretinoin. J Invest Dermatol. 2005; 125 673-684
- 61 Lateef H, Stevens M, Varani J. All-trans retinoic acid suppresses matrix metalloproteinase production/activation and increases collagen synthesis in diabetic skin in organ culture. Am J Pathol. 2004; 165 167-174
- 62 Margelin M, Medaisko C, Lombard D, Picard J, Fountanier A. Hyaluronic acid and dermatan sulfate are selectively stimulated by retinoic acid in irradiated and nonirradiated hairless mouse skin. J Invest Dermatol. 1996; 106 505-515
- 63 Varani J, Warner RL, Phan SH, Datta SC, Fisher GJ, Voorhees JJ. Vitamin A antagonizes decreased cell growth, and elevated collagen-degrading matrix metalloproteinases and stimulates collagen accumulation in naturally-aged human skin. J Invest Dermatol. 2000; 114 480-486
- 64 Kligman AM, Grove GL, Hirose H, Leyden JJ. Topical tretinoin for photoaged skin. J Am Acad Dermatol. 1986; 15 836-859
- 65 Weiss JS, Ellis CN, Headington JT, Tincoff T, Hamilton TA, Voorhees JJ. Topical tretinoin improves photoaged skin: a double-blind, vehicle-controlled study. JAMA. 1988; 259 527-232
- 66 Kligman AM, Dogadkina D, Lavker RM. Effects of topical tretinoin on non-sun-exposed skin of the elderly. J Am Acad Dermatol. 1993; 29 25-33
- 67 Hunt TK, Ehrlich HP, Garcia JA, Dunphy JE. Effect of vitamin A on reversing the inhibitory effect of cortisone on healing of open wounds in animals and man. Ann Surg. 1969; 170 633-641
- 68 Popp C, Kligman AM, Stoudemayer TJ. Pretreatment of photoaged forearm skin with topical tretinoin accelerates healing of full-thickness wounds. Brit J Dermatol. 1995; 132 46-53
- 69 Wicke C, Halliday B, Allen D, Roche NS, Scheuenstuhl H, Spencer MM, Roberts AB, Hunt TK. Effects of steroids and retinoids on wound healing. Arch Surgery. 2000; 135 1265-1270
- 70 Paquette D, Badiavas E, Falanga V. Short-contract topical tretinoin therapy to stimulate granulation tissue in chronic wounds. J Am Acad Dermatol. 2001; 45 382-386
- 71 Holick MF, MacLaughlin JA, Clark MB, Holick SA, Potts JT. Photosynthesis of previtamin D3 in human skin and the physiologic consequences. Science. 1980; 210 203-205
-
72 Reichrath J, Holick MF. Clinical Utility of 1,25-dihydroxyvitamin D3 and its analogs for the treatment of psoriasis and other skin diseases. In: Holick MF (ed).
Vitamin D. Physiology, Molecular Biology and Clinical Applications . Totowa, New Jersey: Humana Press 1999: 357-374 - 73 Lehmann B, Querings K, Reichrath J. Vitamin D and skin: new aspects for dermatology. Exp Dermatol. 2004; 13 ((Suppl 4)) 11-15
- 74 Holick MF. High prevalence of vitamin D inadequacy and implications for health. Mayo Clin Proc. 2006; 81 353-373
- 75 Prosser DE, Jones G. Enzymes involved in the activation and inactivation of vitamin D. Trends Biochem Sci. 2004; 29 664-673
- 76 Ohyama Y, Yamasaki T. Eight cytochrome P450S catalyze vitamin D metabolism. Front Biosci. 2005; 10 608-619
- 77 Matsumoto K, Azuma Y, Kiyoki M, Okumura H, Hashimoto K, Yoshikawa K. Involvement of endogenously produced 1,25-dihydroxyvitamin D-3 in the growth and differentiation of human keratinocytes. Biochim Biophys Acta. 1991; 1092 311-318
- 78 Prystowsky JH, Muzio PJ, Sevran S, Clemens TL. Effect of UVB phototherapy and oral calcitriol (1,25-dihydroxyvitamin D3) on vitamin D photosynthesis in patients with psoriasis. J Am Acad Dermatol. 1996; 35 690-695
- 79 Bikle DD, Gee E. Free, and not total 1,25-dihydroxyvitamin D regulates 25-hydroxyvitamin D metabolism by keratinocytes. Endocrinology. 1989; 124 649-654
- 80 Mendel CM. The free hormone hypothesis: a physiologically based mathematical model. Endocr Rev. 1989; 10 232-274
- 81 Haddad JG. Plasma vitamin D - binding protein (Gc - globulin): multiple tasks. J Steroid Biochem Molec Biol. 1995; 53 579-582
- 82 Bikle DD, Halloran BP, Gee E, Ryzen E, Haddad JG. Free 25-hydroxyvitamin D levels are normal in subjects with liver diseases and reduced total 25-hydroxyvitamin D levels. J Clin Invest. 1986; 78 748-752
- 83 Bikle DD, Nemanic MK, Gee E, Elias P. 1,25-Dihydroxyvitamin D3 production by human keratinocytes. J Clin Invest. 1986; 78 557-566
- 84 Lehmann B, Genehr T, Knuschke P, Pietzsch J, Meurer M. UVB-induced conversion of 7-dehydrocholesterol to 1α,25-dihydroxyvitamin D3 in an in vitro human skin equivalent model. J Invest Dermatol. 2001; 117 1179-1185
- 85 Schuessler M, Astecker N, Herzig G, Vorisek G, Schuster I. Skin is an autonomous organ in synthesis, two-step activation and degradation of vitamin D3: CYP27 in epidermis completes the set of essential vitamin D3-hydroxylases. Steroids. 2001; 66 399-408
-
86 Segaert S, Bouillon R. Epidermal keratinocytes as source and target cells for vitamin D. In: A. Norman W, Bouillon R, Thomasset M (eds).
Vitamin D endocrine system: structural, biological, genetic and clinical aspects. Proceedings of the Eleventh Workshop on Vitamin D, Nashville, TN, USA, May 27-June 1, 2000 . Riverside CA: Printing and Reprographics, University of California 2000: 583-590 - 87 Lehmann B, Sauter W, Knuschke P, Dreßler S, Meurer M. Demonstration of UVB-induced synthesis of 1α,25-dihydroxyvitamin D3 (calcitriol) in human skin by microdialysis. Arch Dermatol Res. 2003; 295 24-28
- 88 Su MJ, Bikle DD, Mancianti ML, Pillai S. 1,25-Dihydroxyvitamin D3 potentiates the keratinocyte response to calcium. J Biol Chem. 1994; 269 14723-14729
- 89 Vantieghem K, De Haes P, Bouillon R, Segaert S. Dermal fibroblasts pretreated with a sterol delta7-reductase inhibitor produce 25-hydroxyvitamin D3 upon UVB irradiation. J Photochem Photobiol. 2006; 85 72-78
- 90 Guryev O, Cavalho RA, Usanov S, Gilep A, Estabrook RW. A pathway for the metabolism of vitamin D3: unique hydroxylated metabolites formed during catalysis with cytochrome P450scc (CYP11A1). Proc Natl Acad Sci USA. 2003; 100 14754-14759
- 91 Slominski A, Zjawiony J, Wortsman J, Semak I, Stewart J, Pisarchik A, Sweatman T, Marcos J, Dunbar C, Tuckey RC. A novel pathway for sequential transformation of 7-dehydrocholesterol and expression of the P450scc system in mammalian skin. Eur J Biochem. 2004; 271 4178-4188
- 92 Carlberg C, Polly P. Gene regulation by vitamin D3. Crit Rev Eukaryot Gene Expr. 1998; 8 19-42
- 93 Chawla A, Repa JJ, Evans RM, Mangelsdorf DJ. Nuclear receptors and lipid physiology: opening the X-files. Science. 2001; 294 1866-1870
- 94 Shaffer PL, Gewirth DT. Structural basis of VDR-DNA interactions on direct repeat response elements. EMBO J. 2002; 21 2242-2252
- 95 Rochel N, Wurtz JM, Mitschler A, Klaholz B, Moras D. Crystal structure of the nuclear receptor for vitamin D bound to its natural ligand. Mol Cell. 2000; 5 173-179
- 96 Moras D, Gronemeyer H. The nuclear receptor ligand-binding domain: structure and function. Curr Opin Cell Biol. 1998; 10 384-391
- 97 Glass CK, Rosenfeld MG. The coregulator exchange in transcriptional functions of nuclear receptors. Genes & Dev. 2000; 14 121-141
- 98 Polly P, Herdick M, Moehren U, Baniahmad A, Heinzel T, Carlberg C. VDR-Alien: a novel, DNA-selective vitamin D3 receptor-corepressor partnership. FASEB J. 2000; 14 1455-1463
- 99 Leo C, Chen JD. The SRC family of nuclear receptor coactivators. Gene. 2000; 245 1-11
- 100 Kwok RPS, Lundblad JR, Chrivia JC, Richards JP, Bächinger HP, Brennan RG, Roberts SGE, Green MR, Goodman RH. Nuclear protein CBP is a coactivator for the transcription factor CREB. Nature. 1994; 370 223-226
- 101 Castillo AI, Jimenez-Lara AM, Tolon RM, Aranda A. Synergistic activation of the prolactin promoter by vitamin D receptor and GHF-1: role of coactivators, CREB-binding protein and steroid hormone receptor coactivator-1 (SRC-1). Mol Endocrinol. 1999; 13 1141-1154
- 102 Rachez C, Suldan Z, Ward J, Chang C-P, Burakov D, Erdjument-Bromage H, Tempst P, Freedman LP. A novel protein complex that interacts with the vitamin D3 receptor in a ligand-dependent manner and enhances transactivation in a cell-free system. Genes & Dev. 1998; 12 1787-1800
- 103 Rachez C, Lemon BD, Suldan Z, Bromleigh V, Gamble M, Näär AM, Erdjument-Bromage H, Tempst P, Freedman LP. Ligand-dependent transcription activation by nuclear receptors requires the DRIP complex. Nature. 1999; 398 824-828
- 104 Carlberg C, Bendik I, Wyss A, Meier E, Sturzenbecker LJ, Grippo JF, Hunziker W. Two nuclear signalling pathways for vitamin D. Nature. 1993; 361 657-660
- 105 MacDonald PN, Dowd DR, Nakajima S, Galligan MA, Reeder MC, Haussler CA, Ozato K, Haussler MR. Retinoid X receptors stimulate and 9-cis retinoic acid inhibits 1,25-dihydroxyvitamin D3-activated expression of the rat osteocalcin gene. Mol Cell Biol. 1993; 13 5907-5917
- 106 Umesono K, Murakami KK, Thompson CC, Evans RM. Direct repeats as selective response elements for the thyroid hormone, retinoic acid, and vitamin D3 receptors. Cell. 1991; 65 1255-1266
- 107 Quack M, Carlberg C. Ligand-triggered stabilization of vitamin D receptor/retinoid X receptor heterodimer conformations on DR4-type response elements. J Mol Biol. 2000; 296 743-756
- 108 Schräder M, Müller KM, Nayeri S, Kahlen JP, Carlberg C. VDR-T3R receptor heterodimer polarity directs ligand sensitivity of transactivation. Nature. 1994; 370 382-386
- 109 Schräder M, Nayeri S, Kahlen JP, Müller KM, Carlberg C. Natural vitamin D3 response elements formed by inverted palindromes: polarity-directed ligand sensitivity of vitamin D3 receptor-retinoid X receptor heterodimer-mediated transactivation. Mol Cell Biol. 1995; 15 1154-1161
- 110 Carlberg C, Mouriño A. New vitamin D receptor ligands. Expert Opin Ther Patents. 2003; 13 761-772
- 111 Liu M, Lee M-H, Cohen M, Bommakanti M, Freedman LP. Transcriptional activation of the Cdk inhibitor p21 by vitamin D3 leads to the induced differentiation of the myelomonocytic cell line U937. Genes & Dev. 1996; 10 142-153
- 112 Xu HM, Tepper CG, Jones JB, Fernandez CE, Studzinski GP. 1,25-Dihydroxyvitamin D3 protects HL60 cells against apoptosis but down-regulates the expression of the bcl-2 gene. Exp Cell Res. 1993; 209 367-374
- 113 Pan Q, Simpson RU. c-myc intron element-binding proteins are required for 1,25-dihydroxyvitamin D3 regulation of c-myc during HL-60 cell differentiation and the involvement of HOXB4. J Biol Chem. 1999; 274 8437-8444
- 114 Jiang H, Lin J, Su Z-z, Collart FR, Huberman E, Fisher PB. Induction of differentiation in human promyelotic HL-60 leukemia cells activates p21, WAF1/CIP1, expression in the absence of p53. Oncogene. 1994; 9 3397-3406
- 115 Albertson DG, Ylstra B, Segraves R, Collins C, Dairkee SH, Kowbel D, Kuo WL, Gray JW, Pinkel D. Quantitative mapping of amplicon structure by array CGH identifies CYP24 as a candidate oncogene. Nat Genet. 2000; 25 144-146
- 116 Lemay J, Demers C, Hendy GN, Delvin EE, Gascon-Barre M. Expression of the 1,25-dihydroxyvitamin D3-24-hydroxylase gene in rat intestine: response to calcium, vitamin D3 and calcitriol administration in vivo. J Bone Miner Res. 1995; 10 1148-1157
- 117 Swami S, Raghavachari N, Muller UR, Bao YP, Feldman D. Vitamin D growth inhibition of breast cancer cells: gene expression patterns assessed by cDNA microarray. Breast Cancer Res Treat. 2003; 80 49-62
- 118 Palmer HG, Sanchez-Carbayo M, Ordonez-Moran P, Larriba MJ, Cordon-Cardo C, Munoz A. Genetic signatures of differentiation induced by 1α,25-dihydroxyvitamin D3 in human colon cancer cells. Cancer Res. 2003; 63 7799-7806
- 119 Gniadecki R. Stimulation versus inhibition of keratinocyte growth by 1,25-Dihydroxyvitamin D3: dependence on cell culture conditions. J Invest Dermatol. 1996; 106 510-516
- 120 Reichrath J, Müller SM, Kerber A, Baum HP, Bahmer FA. Biologic effects of topical calcipotriol (MC 903) treatment in psoriatic skin. J Am Acad Dermatol. 1997; 36 19-28
- 121 Reichrath J, Perez A, Chen TC, Kerber A, Bahmer FA, Holick MF. The effectiveness of topical 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) application in the treatment of psoriasis: an immunohistological evaluation. Acta Derm Venereol (Stockh). 1997; 77 268-272
- 122 Xie SP, Pirianov G, Colston KW. Vitamin D analogues suppress IGF-I signalling and promote apoptosis in breast cancer cells. Eur J Cancer. 1999; 35 1717-1723
- 123 Peng L, Malloy PJ, Feldman D. Identification of a functional vitamin D response element in the human insulin-like growth factor binding protein-3 promoter. Mol Endocrinol. 2004; 18 1109-1119
- 124 Adorini L, Penna G, Giarratana N, Uskokovic M. Tolerogenic dendritic cells induced by vitamin D receptor ligands enhance regulators T cells inhibiting allograft rejection and autoimmune diseases. J Cell Biochem. 2003; 88 227-233
- 125 Griffin M, Kumar R. Effects of 1α,25-Dihydroxyvitamin D3 and its analogs on dendritic cell function. J Cell Biochem. 2003; 88 323-326
- 126 Van Etten E, Decallone B, Verlinden L, Verstuyf A, Bouillon R, Mathieu C. Analogs of 1α,25-Dihydroxyvitamin D3 as pluripotent immunomodulators. J Cell Biochem. 2003; 88 223-226
- 127 Solvoll K, Soyland E, Sandstad B, Drevon CA. Dietary habits among patients with atopic dermatitis. Eur J Clin Nutr. 2000; 54 93-97
- 128 Heine G, Anton K, Henz BM, Worm M. 1alpha,25-dihydroxyvitamin D3 inhibits anti-CD40 plus IL-4-mediated IgE production in vitro. Eur J Immunol. 2002; 32 3395-3404
- 129 Katayama I, Minatohara K, Yokozeki H, Nishioka K. Topical vitamin D3 downregulates IgE-mediated murine biphasic cutaneous reactions. Int Arch Allergy Immunol. 1996; 111 71-76
- 130 Zügel U, Steinmeyer A, Giesen C, Asadullah K. A novel immunosuppressive 1α,25-Dihydroxyvitamin D3 analog with reduced hypercalcemic activity. J Invest Dermatol. 2002; 119 1434-1442
- 131 Tilgen W, Rass K, Reichrath J. 30 Jahre dermatologische Onkologie. Akt Dermatol. 2005; 31 79-88
-
132 Rass K. UV-damage and DNA-repair in basal and squamous cell carcinomas. In: Reichrath J (ed).
Molecular mechanisms of basal cell and squamous cell carcinomas . Landes Bioscience, in press - 133 De Haes P, Garmyn M, Degreef H, Vantieghem K, Bouillon R, Segaert S. 1,25-Dihydroxyvitamin D3 inhibits ultraviolet B-induced apoptosis, Jun kinase activation, and interleukin-6 production in primary human keratinocytes. J Cell Biochem. 2003; 89 663-673
- 134 De Haes P, Garmyn M, Verstuyf A, De Clercq P, Vandewalle M, Vantieghem K, Degreef H, Bouillon R, Segaert S. Two 14-epi analogues of 1,25-dihydroxyvitamin D3 protect human keratinocytes against the effects of UVB. Arch Dermatol Res. 2004; 12 527-534
- 135 De Haes P, Garmyn M, Carmeliet G, Degreef H, Vantieghem K, Bouillon R, Segaert S. Molecular pathways involved in the anti-apoptotic effect of 1,25-dihydroxyvitamin D3 in primary human keratinocytes. J Cell Biochem. 2004; 93 951-967
- 136 De Haes P, Garmyn M, Verstuyf A, De Clercq P, Vandewalle M, Degreef H, Vantieghem K, Bouillon R, Segaert S. 1,25-Dihydroxyvitamin D3 and analogues protect primary human keratinocytes against UVB-induced DNA damage. J Photochem Photobiol B. 2005; 78 141-148
- 137 Dixon KM, Deo SS, Wong G, Slater M, Norman AW, Bishop JE, Posner GH, Ishizuka S, Halliday GM, Reeve VE, Mason RS. Skin cancer prevention: a possible role of 1,25dihydroxyvitamin D3 and its analogs. J Steroid Biochem Mol Biol. 2005; 97 137-143
- 138 Ravid A, Rubinstein E, Gamady A, Rotem C, Liberman UA, Koren R. Vitamin D inhibits the activation of stress-activated protein kinases by physiological and environmental stresses in keratinocytes. J Endocrinol. 2002; 173 525-532
- 139 Diker-Cohen T, Koren R, Liberman UA, Ravid A. Vitamin D protects keratinocytes from apoptosis induced by osmotic shock, oxidative stress, and tumor necrosis factor. Ann N Y Acad Sci. 2003; 1010 350-353
- 140 Gombard HF, Borregaard N, Koeffler HP. Human cathelicidin antimicrobial peptide (CAMP) gene is a direct target of the vitamin D receptor and is strongly up-regulated in myeloid cells by 1,25-dihydroxyvitamin D3. FASEB J. 2005; 19 1067-1077
- 141 Wang T-T, Nestel FP, Bourdeau V, Nagai Y, Wang Q, Liao J, Tavera-Mendoza L, Lin R, Hanrahan JH, Mader S, White JH. Cutting Edge: 1,25-Dihydroxyvitamin D3 is a direct inducer of antimicrobial peptide gene expression. J Immunol. 2004; 173 2909-2912
- 142 Weber G, Heilborn JD, Chamorro Jimenez CI, Hammarsjö A, Törmä H, Ståhle M. Vitamin D Induces the Antimicrobial Protein hCAP18 in Human Skin. J Invest Dermatol. 2005; 124 1080-1082
- 143 Reichrath J. Will analogs of 1,25-dihydroxyvitamin D3 (calcitriol) open a new era in cancer therapy?. Onkologie. 2001; 24 128-133
Correspondence
C. C. Zouboulis
Departments of Dermatology and Immunology
Dessau Medical Center
Auenweg 38
06847 Dessau
Germany
Telefon: +49/340/501 40 00
Fax: +49/340/501 40 25
eMail: christos.zouboulis@klinikum-dessau.de