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Expression of retinoid-X receptors (-· ,-· ,-·) and retinoic acid receptors (-· ,-· ,-·) in normal human skin: an immunohistological evaluation

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Summary

Increasing evidence suggests that the retinoid-X receptors (RXR-· ,-· ,-·) play a crucial role in regulating the transcriptional activity of several steroid hormone receptors, including the receptors for retinoic acid (RAR-· ,-· ,-·), 1,25-dihydroxyvitamin D3 and thyroid hormone. We investigated the localization of the different types of RXR-· ,-· ,-· and RAR-· ,-· ,-· proteins in frozen sections of normal human skin (n = 12) in situ, applying recently raised corresponding specific monoclonal antibodies and an immunohistochemical technique that we established for the detection of these nuclear receptors. Our findings indicate that RXR-· ,-· ,-· and RAR-· ,-· ,-· proteins can be detected by immunohistochemistry in normal human skin. In contrast to RXR-· ,-· ,-· as well as RAR-· and RAR-· proteins that were consistently detected in cell layers of the viable epidermis, RAR-· was only focally demonstrated in single epidermal cells in three out of 12 biopsies analysed. Immunohistochemical labelling of RAR-· ,-· ,-· and RXR-· ,-· ,-· proteins in epidermal nuclei was also pronounced in the stratum granulosum, suggesting a function of RXR and RAR proteins in the transition from proliferation to differatiation in epidermal keratinocytes. Expression of RXRs and RARs in hair follicles, sebaceous glands and endothelial cell points to a biological function from these nuclear receptors to hair growth as well as to the physiology of sebaceous glands and endothelial cells.

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References

  • Carlberg, C., Bendik, I., Wyss, A., Meier, E., Sturzenbecker, L.J., Grippo, J.F. & Hunziker, W. (1993) Two nuclear signalling pathways for vitamin D. Nature 361, 657-60.

    Article  PubMed  CAS  Google Scholar 

  • Connor, M.J. & Lowe, N. (1983) The induction of ornithine decarboxylase activity and DNA synthesis in hairless mouse epidermis by retinoids. Cancer Res. 43, 5174-7.

    PubMed  CAS  Google Scholar 

  • Ehmann, C.W. & Voorhees, J.J. (1982) International studies of the efficacy of etretinate in the treatment of psoriasis. J. Am. Acad. Dermatol. 6, 692-6.

    Article  PubMed  CAS  Google Scholar 

  • Elder, J.T., Fisher, G.J., Zhang, Q.Y., Eisen, D., Krust, A., Kastner, P., Chambon, P. & Voorhees J.J. (1991) Retinoic acid receptor gene expression in human skin. J. Invest. Dermatol. 96, 425-33.

    Article  PubMed  CAS  Google Scholar 

  • Elder, J.T., AstrÖm, A., Petterson, U., Tavakkol, A., Griffiths, C.E., Krust, A., Kastner, P., Chambon, P. & Voorhees, J.J. (1992a) Differential regulation of retinoic acid receptors and binding proteins in human skin. J. Invest. Dermatol. 98(5), 673-9.

    Article  PubMed  CAS  Google Scholar 

  • Elder, J.T., AstrÖm, A., Petterson, U., Tavakkol, A., Krust, A., Kastner, P., Chambon, P. & Voorhees, J.J. (1992b) Retinoid acid receptors and binding proteins in human skin. J. Invest. Dermatol. 98(6), 36S-41S.

    Article  PubMed  CAS  Google Scholar 

  • Evans, R. (1988) The steroid and thyroid hormone receptor family. Science 240, 889-95.

    Article  PubMed  CAS  Google Scholar 

  • Fisher, G.J., Esmann, J., Griffiths, C.E., Talwar, H.S., Duell, E.A., Hammerberg, C., Elder, J.T., Finkel, L.F., Karabin, G.D. & Nickoloff, B.J. (1991) Cellular, immunologic and biochemical characterization of topical retinoic acid-treated human skin. J. Invest. Dermatol. 96, 699-707.

    Article  PubMed  CAS  Google Scholar 

  • Fisher, G.J., Talwar, H.S., Xiao, J.H., Datta, S.C., Reddy, A.P., Gaub, M.P., Rochette-Egly, C., Chambon, P. & Voorhees, J.J. (1994) Immunological identification and functional quantitation of retinoic acid and retinoid x receptor proteins in human skin. J. Biol. Chem. 269, 20629-35.

    PubMed  CAS  Google Scholar 

  • Gaub, M.P., Lutz, Y., Ruberte, E., Petkovich, M., Brand, N. & Chambon, P. (1989) Antibodies specific to the retinoic acid human nuclear receptors · and ·. Proc. Natl Acad. Sci. USA 86, 3089-93.

    Article  PubMed  CAS  Google Scholar 

  • Gaub, M.P., Rochette-Egly, C., Lutz, Y., Ali, S., Matthes, H., Scherer, I. & Chambon, P. (1992) Immunodetection of multiple species of retinoic acid receptor alpha: evidence for phosphorylation. Exp. Cell. Res. 201, 335-46.

    Article  PubMed  CAS  Google Scholar 

  • Glass, C.K., Lipkin, S.M., Devary, O.V. & Rosenfeld, M.G. (1989) Positive and negative regulation of gene transcription by a retinoic acid-thyroid hormone receptor heterodimer. Cell 59, 697-708.

    Article  PubMed  CAS  Google Scholar 

  • Green, S. (1993) Promiscuous liaisons. Nature 361, 590-1.

    Article  PubMed  CAS  Google Scholar 

  • Green, S. & Chambon, P. (1988) Nuclear receptors enhance our understanding of transcription regulation. Trends Genet. 4, 309-14.

    Article  PubMed  CAS  Google Scholar 

  • Gudas, L.J., Sporn, M.B. & Roberts, A.B. (1994) Cellular biology and biochemistry of the retinoids. In Retinoids: Biology, Chemistry and Medicine (edited by Sporn, M.B., Roberts, A.B. & Goodman, D.S.), 2nd edn, pp. 443-520. New York: Raven Press.

    Google Scholar 

  • Heyman, R.A., Mangelsdorf, D.J., Dyck, J.A., Stein, R.B., Eichele, G., Evans, R.M. & Thaller, C. (1992) 9-cis retinoic acid is a high affinity ligand for the retinoid X receptor. Cell 68, 397-406.

    Article  PubMed  CAS  Google Scholar 

  • Hofman, C. & Eichele, G. (1994) Retinoids in development. In Retinoids: Biology, Chemistry and Medicine (edited by Sporn, M.B., Roberts, A.B. & Goodman, D.S.), 2nd edn, pp. 387-441. New York: Raven Press.

    Google Scholar 

  • Kliewer, S.A., Umesono, K., Mangelsdorf, D.J. & Evans, R.M. (1992) Retinoid X receptor interacts with nuclear receptors in retinoid acid, thyroid hormone and vitamin D3 signaling. Nature 355, 446-9.

    Article  PubMed  CAS  Google Scholar 

  • Leid, M., Kastner, P., Lyons, R., Nakshatri, H., Saunders, M., Zacharewski, T., Chen, J., Staub, A., Garnier, J., Mader, S. & Chambon, P. (1992) Purification, cloning and RXR identity of the HeLa cell factor with which RAR or TR heterodimerizes to bind target sequences efficiently. Cell 68, 377-95.

    Article  PubMed  CAS  Google Scholar 

  • Lichti, U., Ben, T. & Yuspa, S.H. (1985) Retinoic acid-induced transglutaminase in mouse epidermal cells is distinct from epidermal transglutaminase. J. Biol. Chem. 260, 1422-6.

    PubMed  CAS  Google Scholar 

  • Lowe, N.J., Kaplan, R. & Breeding, J. (1982) Etretinate treatment for psoriasis inhibits epidermal ornithine decarboxylase. J. Am. Acad. Dermatol. 6, 697-8.

    Article  PubMed  CAS  Google Scholar 

  • Mangelsdorf, D.J., Borgmeyer, U. & Heyman, R.A. (1992) Characterization of three RXR genes that mediate the action of 9-cis retinoic acid. Genes Dev. 6, 329-44.

    Article  PubMed  CAS  Google Scholar 

  • Peck, G.L. & Digiovanna, J.J. (1994) Synthetic retinoids in dermatology. In Retinoids: Biology, Chemistry and Medicine (edited by Sporn, M.B., Roberts, A.B. & Goodman, D.S.), 2nd edn, pp. 631-58. New York: Raven Press.

    Google Scholar 

  • Rees, J.L. & Redfern, C.P. (1989) Expression of the alpha and beta retinoic acid receptors in skin. J. Invest. Dermatol. 93, 818-20.

    Article  PubMed  CAS  Google Scholar 

  • Reichrath, J., MÜnssinger, T., Kerber, A., Rochette-Egly, C., Chambon, P., Bahmer, F.A. & Baum, H.-P. (1995) In situ detection of retinoid-X receptor expression in normal and psoriatic human skin. Br. J. Dermatol. 133, 168-75.

    Article  PubMed  CAS  Google Scholar 

  • Rochette-Egly, C., Lutz, Y., Saunders, M., Scheuer, I., Gaub, M.P. & Chambon, P. (1991) Retinoic acid receptor ·: specific immunodetection and phosphorylation. J. Cell. Biol. 115, 535-45.

    Article  PubMed  CAS  Google Scholar 

  • Rochette-Egly, C., Gaub, M.P., Lutz, Y., Ali, S., Scheuer, I. & Chambon, P. (1992) Retinoic acid receptor-beta: immunodetection and phosphorylation on tyrosine residues. Mol. Endocrinol. 12, 2197-206.

    Article  Google Scholar 

  • Rochette-Egly, C., Lutz, Y., Pfister, V., Heyberger, S., Scheuer, I., Chambon, P. & Gaub, M.P. (1994) Detection of retinoid X receptors using specific monoclonal and polyclonal antibodies. Biochem. Biophys. Res. Commun. 204, 525-36.

    Article  PubMed  CAS  Google Scholar 

  • Ross, A.C. & HÄmmerling, U.G. (1994) Retinoids and the immune system. In Retinoids: Biology, Chemistry and Medicine (edited by Sporn, M.B., Roberts, A.B. & Goodman, D.S.), 2nd edn, pp. 521-44. New York: Raven Press.

    Google Scholar 

  • Sofen, H.L., Moy, R.L. & Lowe, N.J. (1984) Treatment of generalized pustular psoriasis with isotretinoin. Lancet 1, 40.

    Article  PubMed  CAS  Google Scholar 

  • Summerbell, D. & Maden, M. (1990) Retinoic acid, a developmental signalling molecule. Trends Neurosci. 13, 142-7.

    Article  PubMed  CAS  Google Scholar 

  • Ward, A., Brogden, R.N., Hell, R.C., Speight, T.M. & Avery, G.S. (1983) Etretinate. A review of its pharmacological properties and therapeutic efficacy in psoriasis and other skin disorders. Drugs 26, 9-43.

    Article  PubMed  CAS  Google Scholar 

  • Yaar, M., Stanley, J.R. & Katz, S.I. (1981) Retinoic acid delays the terminal differentiation of keratinocytes in suspension culture. J. Invest. Dermatol. 76, 363-6.

    Article  PubMed  CAS  Google Scholar 

  • Yu, V.C., Deisert, C., Andersen, B., Holloway, J.M., Devary, O.V., NÄÄr, A.M., Kim, S.Y., Boutin, J.M., Glass, C.K. & Rosenfeld, M.G. (1991) RXR: A coregulator that enhances binding of retinoic acid, thyroid hormone and vitamin D receptors to their cognate response elements. Cell 67, 1251-66.

    Article  PubMed  CAS  Google Scholar 

  • Zhang, X.K., Lehmann, J., Hoffmann, B., Dawson, M.I., Cameron, J., Graupner, G., Hermann, T., Tran, P. & Pfahl, M. (1992) Homodimer formation of retinoid X receptor induced by 9-cis retinoic acid. Nature 358, 587-91.

    Article  PubMed  CAS  Google Scholar 

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Reichrath, J., Mittmann, M., Kamradt, J. et al. Expression of retinoid-X receptors (-· ,-· ,-·) and retinoic acid receptors (-· ,-· ,-·) in normal human skin: an immunohistological evaluation. J Mol Hist 29, 127–133 (1997). https://doi.org/10.1023/A:1026481205135

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