Skip to main content
SpringerLink
Log in

The increase in skin 7-dehydrocholesterol induced by an hypocholesterolemic agent is associated with elevated 25-hydroxyvitamin D3 plasma level

  • Transport Processes, Metabolism and Endocrinology; Kidney, Gastrointestinal Tract, and Exocrine Glands
  • Published:
Pflügers Archiv Aims and scope Submit manuscript

Abstract

Vitamin D3 is generated in skin by UV irradiation of 7-dehydrocholesterol (7-DEHC). Whether the 7-DEHC amount in skin affects vitamin D3 formation, and thereby the plasma level of 25-hydroxyvitamin D3 (25[OH]D3) is not known. In the present work we report on the influence on vitamin D and Ca metabolism of a new hypocholesterolemic agent, HCG-917 (0-2-[hydroxy-3-]N′-(2-chlorophenyl)-N-piperazinyl-1-[propyl]-4-chloro-benz-aldoxim-hydrochloride) which inhibits 7-DEHC reductase and thereby increases skin 7-DEHC. Rats were treated with HCG 917 (0.3 and 5.0 mg/kg, orally) for 13 days. HCG 917 caused a dose-dependent decrease in cholesterol and concomitant accumulation of 7-DEHC in plasma and skin. In skin, 7-DEHC was: control: 1.05±0.20; HCG 917, 0.3 mg/kg: 1.41±0.22; HCG 917, 5.0 mg/kg: 2.35±0.35 mg/g. At a dose of 0.3 mg/kg, HCG 917 had no significant influence on the plasma level of neither 25(OH)D3 nor 1,25(OH)2D3. However, at a dose of 5.0 mg/kg, HCG 917 induced a significant increase in plasma 25(OH)D3 (control: 36.2±2.2; HCG 917 5.0 mg/kg: 57.6±6.5 nmol/l) and a slight but not significant rise in 1,25(OH)2D3. Calcium balance studies indicated that HCG 917 did not influence intestinal Ca absorption nor urinary Ca excretion. At a dose of 5.0 mg/kg HCG 917 slightly induced a decrease in total plasma Ca. In conclusion, HCG 917 treatment can induce a significant rise in skin 7-DEHC with an increase in plasma 25(OH)D3. These results suggest that variation in the skin level of 7-DEHC can directly influence the cutaneous production of vitamin D3 and thereby the vitamin D status of the organism.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Bonjour JP, Trechsel U, Fleisch H, Schenk R, DeLuca HF, Baxter LA (1975) Action of 1,25-dihydroxyvitamin D3 and a diphosphonate on calcium metabolism in rats. Am J Physiol 229:402–408

    Google Scholar 

  2. Clemens TL, Adams JS, Horiuchi N, Gilchrest BA, Cho H, Tsuchiya Y, Matsuo N, Suda T, Holick MF (1983) Interaction of 1,25-dihydroxyvitamin D3 with keratinocytes and fibroblasts from skin of normal subjects and a subject with vitamin D-dependent rickets, type II: a model for study of the mode of action of 1,25-dihydroxyvitamin D3. J Clin Endocrinol Metab 56:824–830

    Google Scholar 

  3. Curtis HC, Burgi W (1966) Gaschromatographische Bestimmung des Serumcholesterins. Z Klin Chem 4:38–42

    Google Scholar 

  4. Eil C, Marx SJ (1981) Nuclear uptake of 1,25-dihydroxy[3H]-cholecalciferol in dispersed fibroblasts cultured from normal human skin. Proc Natl Acad Sci USA 78:2562–2566

    Google Scholar 

  5. Eisman JA, Hamstra AJ, Kream BE, DeLuca HF (1976) A sensitive, precise, and convenient method for determination of 1,25-dihydroxyvitamin D in human plasma. Arch Biochem Biophys 176:235–243

    Google Scholar 

  6. Esvelt RP, Schnoes HR, DeLuca HF (1978) Vitamin D3 from rat skins irradiated in vitro with ultraviolet light. Arch Biochem Biophys 188:282–286

    Google Scholar 

  7. Feldman D, Chen T, Hirst M, Colston K, Karasek M, Cone C (1980) Demonstration of 1,25-dihydroxyvitamin D3 receptor in human skin biopsies. J Clin Endocrinol Metab 51:1463–1465

    Google Scholar 

  8. Folch J, Lees M, Sloane-Stanley GH (1957) A simple method for the isolation and purification of total lipids from animal tissues. J Biol Chem 226:497–509

    Google Scholar 

  9. Fraser DR (1983) The physiological economy of vitamin D. Lancet i:969–972

    Google Scholar 

  10. Holick MF (1985) Vitamin D photobiology: Recent advances in the biochemistry and some clinical applications. In: Norman AW, Schaefer K, Grigoleit HG, Herrath DV (eds) Vitamin D, a chemical, biochemical and clinical update. de Gruyter, Berlin New York, pp 219–228

    Google Scholar 

  11. Holick MF, Clark MB (1978) The photobiogenesis and metabolism of vitamin D. Fed Proc 37:2567–2574

    Google Scholar 

  12. Holick MF, MacLaughlin JA, Clark MB, Holick SA, Potts JT Jr, Anderson RR, Blank IH, Parrish JA, Elias P (1980) Photosynthesis of previtamin D3 in human skin and the physiological consequences. Science 210:203–205

    Google Scholar 

  13. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275

    Google Scholar 

  14. Preece MA, O'Riordan JLH, Lawson DEM, Kodicek E (1974) A competitive protein-binding assay for 25-hydroxycholecalciferol and 25-hydroxyergocalciferol in serum. Clin Chim Acta 54:235–242

    Google Scholar 

  15. Simpson RU, DeLuca HF (1980) Characterization of a receptor-like protein for 1,25-dihydroxyvitamin D3 in rat skin. Proc Natl Acad Sci USA 77:5822–5826

    Google Scholar 

  16. Suda T, Miyaura C, Abe E, Kuroki T (1986) Modulation of cell differentiation, immune response and tumor promotion by vitamin D compounds. In: Peck WA (ed) Bone and mineral research 4. Elsevier, Amsterdam New York, pp 1–48

    Google Scholar 

  17. Trechsel U, Eisman JA, Fischer JA, Bonjour JP, Fleisch H (1980) Calcium-dependent, parathyroid hormone-independent regulation of 1,25-dihydroxyvitamin D. Am J Physiol 239: E119-E124

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Pathophysiology, Department of Medicine, University Hospital, CH-1211, Geneva 4, Switzerland

    J. -P. Bonjour

  2. Pathophysiologisches Institut, University of Berne, CH-3010, Berne, Switzerland

    U. Trechsel

  3. Hoechst AG, D-6000, Frankfurt, Federal Republic of Germany

    E. Granzer, G. Klöpffer, K. Müller & D. Scholler

  4. Ciba-Geigy Limited, CH-4000, Basel, Switzerland

    E. Granzer, G. Klöpffer, K. Müller & D. Scholler

Authors
  1. J. -P. Bonjour
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. U. Trechsel
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. E. Granzer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. G. Klöpffer
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. K. Müller
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. D. Scholler
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bonjour, J.P., Trechsel, U., Granzer, E. et al. The increase in skin 7-dehydrocholesterol induced by an hypocholesterolemic agent is associated with elevated 25-hydroxyvitamin D3 plasma level. Pflugers Arch. 410, 165–168 (1987). https://doi.org/10.1007/BF00581910

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00581910

Key words

Search

Navigation