Original Article

Journal of Investigative Dermatology (1984) 83, 110–113; doi:10.1111/1523-1747.ep12263280

Topical and Systemic Effects of Retinoids on Horn-Filled Utriculus Size in the Rhino Mouse. A Model to Quantify "Antikeratinizing" Effects of Retinoids

James A Mezick, Meena C Bhatia and Robert J Capetola

Research Laboratories, Ortho Pharmaceutical Corporation, Raritan, New Jersey, U.S.A.

Received 12 January 1984; Accepted 3 April 1984.

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Abstract

A method was developed to quantify the "antikeratinizing" effects of various retinoids (all-trans-retinoic acid, 13-cis-retinoic acid, motretinide, etretinate) in rhino mouse skin, which contains many keratinized pilosebaceous structures or horn-filled utriculi. Mean utriculus diameters in whole mount epidermis were determined and dose-response relationships were constructed after topical or oral administration of test retinoids. All- trans-retinoic acid was 3.7times, 12.5times, and 50times more potent than 13-cis-retinoic acid, etretinate, and motretinide, respectively, after topical administration. Administered orally, all-trans-retinoic acid was 2.3times more potent than 13-cis-retinoic acid At 5 mg/kg, each retinoid produced a significant reduction in utriculus size. The rhino mouse model represents a novel and useful assay to quantify antikeratinizing activity and potency differences of biologically active retinoids.

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References

  1. Lotan, R: Effects of vitamin A and its analogs (retinoids) on normal and neoplastic cells. Biochim Biophys Acta 1980 605: 33–91,  | Article | PubMed | ISI | ChemPort |
  2. Elias, PM, Fritsch, PO, Lampe, M, Williams, ML, Brown, BE, Nemanic, M, Grayaon, SG: Retinoid effects on epidermal structur, differentiation, and permeability. Lab Invest 1981 44: 531–540,  | PubMed | ISI | ChemPort |
  3. Kubilus, J: Modulation of differentiation by retinoids. J Invest Dermatol 1983 81: 55–58,  | Article |
  4. Elias, PM, Wiliams, ML: Retinoids, cancer and the skin. Arch Dermatol 1981 117: 160–180,  | Article | PubMed | ChemPort |
  5. Peck, GL: Retinoids in clinical dermatology, Progress in Diseases of the Skin 1981 1: Edited by R Fleischmajer. New York, Grune & Stratton, pp 227–269,
  6. Kligman, AM, Fulton, JE, Plewig, G: Topical vitamin A acid in acne vulgaris. Arch Dermatol 1969 99: 469–476,  | Article | PubMed | ISI | ChemPort |
  7. Papa, CM: Vitamin A acid topical therapy, Acne Update for the Practitioner 1977 Edited by SB Frank. New York, Yorke Medical Books, pp 121–135,
  8. Peck, GL, Olsen, TG, Yoder, FW, Strauss, JS, Downing, DT, Pandya, M, Butkus, D, Arnaud-Battandier, J: Prolonged remissions of cystic acne and conglobate acne with 13-cis-retinoic acid. N Engl J Med 1979 300: 329–333,  | PubMed | ISI | ChemPort |
  9. Peck, GL, Olsen, TG, Butkus, D, Pandya, M, Arnaud-Battandier, J, Gross, EG, Windhorst, DB, Cheripko, J: Isotretinoin versus pla- cebo in the treatment of cystic acne. J Am Acad Dermatol 1982 6: 735–745,  | PubMed | ChemPort |
  10. Peck, GL, Gross, EG, Butkus, D: Comparative analysis of two retinoids in the treatment of disorders of keratinization, Retinoids: Advances in Basic Research and Therapy 1981 Edited by CE Orfanos, O Braun-Falco, EM Farber, Ch Grupper, MK Polano, R. Schuppli. New York, Springer-Verlag, pp 279–286,
  11. Goldsmith, LA, Weinrich, AE, Shupack, J: Pityriasis rubra pilaris response to 13-cis-retinoic acid (isotretinoin). J Am Acad Dermatol 1982 6: 710–715,  | PubMed | ChemPort |
  12. Baden, HP, Buxman, MM, Weinstein, GD, Yoder, FW: Treatment of ichthyosis with isotretinoin. J Am Acad Dermatol 1982 6: 716–720,  | PubMed | ChemPort |
  13. Dicken, CH, Bauer, EA, Hazen, PG, Krueger, GG, Marks, JG Jr, McGuire, JS, Schachner, LA: Isotretinoin treatment of Darier's disease. J Am Acad Dermatol 1982 6: 721–726,  | PubMed | ChemPort |
  14. Christiansen, J, Holm, P, Reymann, F: The retinoic acid derivative Ro 11-1430 in acne vulgaris. Dermatologica 1977 154: 219–227,  | PubMed | ChemPort |
  15. Nordin, K, Fredriksson, T, Rylander, C: Ro 11–1430, a new retinoic acid derivative for the topical treatment of acne. Dermatologica 1981 162: 104–111,  | PubMed | ChemPort |
  16. Ott, F, Bollag, W: Therapie der Psoriasis mit einem oral wirksamen neuen vitamin-A-saure Derivat. Schweiz Med Wochenschr 1975 105: 439–441,  | PubMed | ChemPort |
  17. Ehmann, CW, Voorhees, JJ: International studies of the efficacy of etretinate in the treatment of psoriasis. J Am Acad Dermatol 1982 6: 692–696,  | PubMed | ISI | ChemPort |
  18. Baden, HP, Kuhilus, J, Rand, R: Quantitative effects of retinoids on the cultured human keratinocyte (abstr). J Invest Dermatol 1981 76: 313,
  19. Yuspa, S, Ben, T, Steinert, P: Retinoic acid induces transglutaminase activity but inhibits cornification of cultured epidermal cells. J Biol Chem 1982 257: 9906–9908,  | PubMed | ISI | ChemPort |
  20. Yaar, M, Stanley, JR, Katz, SI: Retinoic acid delays the terminal differentiation of keratinocytes in suspension culture. J Invest Dermatol 1981 76: 363–366,  | Article | PubMed | ChemPort |
  21. Newton, DL, Henderson, WR, Sporn, MB: Structure-activity relationships of retinoids in hamster tracheal organ culture. Cancer Res 1980 40: 3413–3425,  | PubMed | ChemPort |
  22. Spearman, RIC, Jarrett, A: Biological comparison of isomers andchemical forms of vitamin A (retinol). Br J Dermatol 1974 90: 553–560,  | PubMed | ChemPort |
  23. Mann, SJ: Hair loss and cyst formation in hairless and rhino mutantmice. Anat Rec 1971 170: 485–500,  | Article | PubMed | ISI | ChemPort |
  24. Van Scott, EJ: Experimental animal integumental models forscreening potential dermatologic drugs, Pharmacology of the kin 1972 Edited by W Montagna, EJ Van Scott, R Stoughton. New York, Appleton-Century-Crofts, pp 523–533,
  25. Kligman, LH, Kligman, AM: The effect on rhino mouse skin of agents which influence keratinization and exfoliation. J Invest Dermatol 1979 73: 354–358,  | Article | PubMed | ISI | ChemPort |
  26. Finney, DJ: Parallel line assays. Statistical Method in Biological Assay 1978 3d ed. London, Charles Griffin & Company Ltd, pp 69–104,
  27. Dunnett, CW: A multiple comparison procedure for comparing several treatments with a control. J Am Stat Assoc 1955 50: 1096–1121,  | Article | ISI |
  28. Plewig, G, Nikolowski, J, Wolff, HH: Action of isotretinoin in acne rosacea and gram-negative folliculitis. J Am Acad Dermatol 1982 6: 766–785,  | PubMed | ChemPort |
  29. Mezick, JA, Chhabria, MC, Thorne, EG, Capetola, RJ: Topical and oral (p.o.) effects of 13-cis-retinoic acid (13-cis-RA) and all- trans-retinoic acid (RA) on horn-filled utriculi (pseudocome- dones) size in the rhino mouse (abstr). J Invest Dermatol 1982 78: 350,

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