A melanocortin receptor 1 and 5 antagonist inhibits sebaceous gland differentiation and the production of sebum-specific lipids

Journal of Dermatological Science

Volumn 63, Issue 1, 2011, Pages 23-32

  Eisinger, Magdalena ^a   Li, Wen Hwa ^a   Anthonavage, Michael ^a   Pappas, Apostolos ^a   Zhang, Li ^a   Rossetti, Dianne ^a   Huang, QiuLing ^a   Seiberg, Miri ^a  

^a JOHNSON AND JOHNSON   (United States)

Author keywords

Antagonist; Lipids; Melanocortin receptor 5; Sebaceous gland differentiation; Sebum

Indexed keywords

EPITHELIAL MEMBRANE ANTIGEN; FLUTAMIDE; HORMONE RECEPTOR BLOCKING AGENT; JNJ 10229570; MELANOCORTIN 1 RECEPTOR; MELANOCORTIN 5 RECEPTOR; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANTIGEN EXPRESSION; ARTICLE; CELL DIFFERENTIATION; CONTROLLED STUDY; HUMAN; HUMAN CELL; HUMAN TISSUE; LIPOGENESIS; MALE; MOUSE; NONHUMAN; ORGAN SIZE; PRIORITY JOURNAL; PROTEIN FUNCTION; SEBACEOUS GLAND; SEBUM SECRETION;

ADMINISTRATION, CUTANEOUS; ANIMALS; CELL DIFFERENTIATION; CELLS, CULTURED; CYCLIC AMP; DOSE-RESPONSE RELATIONSHIP, DRUG; FLUTAMIDE; GENE EXPRESSION REGULATION; HORMONE ANTAGONISTS; HUMANS; LIPID METABOLISM; MALE; MICE; MICE, SCID; MUCIN-1; RECEPTOR, MELANOCORTIN, TYPE 1; RECEPTORS, MELANOCORTIN; SEBACEOUS GLANDS; SEBUM; SKIN TRANSPLANTATION; TRANSPLANTATION, HETEROLOGOUS;

EID: 79957540676     PISSN: 09231811     EISSN: 1873569X     Source Type: Journal    
DOI: 10.1016/j.jdermsci.2011.04.001     Document Type: Article

References (53)

1. Smith K.R., Thiboutot D.M. Thematic review series: skin lipids. Sebaceous gland lipids: friend or foe?. J Lipid Res 2008, 49:271-281.
2. Pappas A. Epidermal surface lipids. Dermatoendocrinology 2009, 1:72-76.
3. Zouboulis C.C. Acne and sebaceous gland function. Clin Dermatol 2004, 22:360-366.
4. Zouboulis C.C., Schagen S., Alestas T. The sebocyte culture: a model to study the pathophysiology of the sebaceous gland in sebostasis, seborrhoea and acne. Arch Dermatol Res 2008, 300:397-413.
5. Thiboutot D., Gollnick H., Bettoli V., Dréno B., Kang S., Leyden J.J., et al. New insights into the management of acne: an update from the global alliance to improve outcomes in acne group. J Am Acad Dermatol 2009, 60:S1-50.
6. Kurokawa I., Danby F.W., Ju Q., Wang X., Xiang L.F., Xia L., et al. New developments in our understanding of acne pathogenesis and treatment. Exp Dermatol 2009, 18:821-832.
7. Zouboulis C.C., Degitz K. Androgen action on human skin - from basic research to clinical significance. Exp Dermatol 2004, 13Suppl4:5-10.
8. Makrantonaki E., Vogel K., Fimmel S., Oeff M., Seltmann H., Zouboulis C.C. Interplay of IGF-I and 17β-estradiol at age-specific levels in human sebocytes and fibroblasts in vitro. Exp Gerontol 2008, 43:939-946.
9. Cone R.D. Studies on the physiological functions of the melanocortin system. Endocr Rev 2006, 27:736-749.
10. Thody A.J., Shuster S. Possible role of MSH in the mammal. Nature 1973, 245:207-209.
11. Ebling F.J., Ebling E., Randall V., Skinner J. The effects of hypophysectomy and of bovine growth hormone on the responses to testosterone of prostate, preputial, Harderian and lachrymal glands and of brown adipose tissue in the rat. J Endocrinol 1975, 66:401-406.
12. Thody A.J., Cooper M.F., Bowden P.E., Meddis D., Shuster S. Effect of alpha-melanocyte-stimulating hormone and testosterone on cutaneous and modified sebaceous glands in the rat. J Endocrinol 1976, 71:279-288.
13. Zhang L., Anthonavage M., Huang Q., Li W.H., Eisinger M. Proopiomelanocortin peptides and sebogenesis. Ann N Y Acad Sci 2003, 994:154-161.
14. Bohm M., Luger T.A., Tobin D.J., Garcia-Borron J.C. Melanocortin receptor ligands: new horizons for skin biology and clinical dermatology. J Invest Dermatol 2006, 126:1966-1975.
15. Slominski A., Ermak G., Mihm M. ACTH receptor, CYP11A1, CYP17 and CYP21A2 genes are expressed in skin. J Clin Endocrinol Metab 1996, 81:2746-2749.
16. Bohm M., Luger T.A. Melanocortins in fibroblast biology-current update and future perspective for dermatology. Exp Dermatol 2004, 13:16-21.
17. Zhang L., Li W.H., Anthonavage M., Eisinger M. Melanocortin-5 receptor: a marker of human sebocyte differentiation. Peptides 2006, 27:413-420.
18. Thiboutot D., Sivarajah A., Gilliland K., Cong Z., Clawson G. The melanocortin 5 receptor is expressed in human sebaceous glands and rat preputial cells. J Invest Dermatol 2000, 115:614-619.
19. Bohm M., Schiller M., Stander S., Seltmann H., Li Z., Brzoska T., et al. Evidence for expression of melanocortin-1 receptor in human sebocytes in vitro and in situ. J Invest Dermatol 2002, 118:533-539.
20. Chen W., Kelly M.A., Opitz-Araya X., Thomas R.E., Low M.J., Cone R.D. Exocrine gland dysfunction in MC5-R-deficient mice: evidence for coordinated regulation of exocrine gland function by melanocortin peptides. Cell 1997, 91:789-798.
21. Thody A.J., Shuster S. Control and function of sebaceous glands. Physiol Rev 1989, 69:383-416.
22. Clarke S.B., Nelson A.M., George R.E., Thiboutot D.M. Pharmacologic modulation of sebaceous gland activity: mechanisms and clinical applications. Dermatol Clin 2007, 25:137-146.
23. Wang H.-S., Wang T.-H., Soong Y.-K. Low dose flutamide in the treatment of Acne vulgaris in women with or without oligomenorrhea or amenorrhea. Chang Gung Med J 1999, 22:423-432.
24. Pan K., Scott M.K., Lee D.H., Fitzpatrick L.J., Crooke J.J., Rivero R.A., et al. 2,3-Diaryl-5-anilino[1,2,4]thiadiazoles as melanocortin MC4 receptor agonists and their effects on feeding behavior in rats. Bioorg Med Chem 2003, 11:185-192.
25. Huang Q., Anthonavage M., Li W.H., Eisinger M. The role of α-MSH in human sebaceous lipogenesis. J Invest Dermatol 2002, 119:275.
26. McMillian M.K., Grant E.R., Zhong Z., Parker J.B., Li L., Zivin R.A., et al. Nile red binding to HepG2 cells: an improved assay for in vitro studies of hepatosteatosis. In Vitr Mol Toxicol 2001, 14:177-190.
27. Zouboulis C.C., Seltmann H., Hiroi Naoki, Chen W.C., Young M., Oeff M., et al. Corticotropin-releasing hormone: an autocrine hormone that promotes lipogenesis in human sebocytes. PNAS 2002, 99:7148-7153.
28. Eisinger M., Li W.H., Rossetti D., Anthonavage M., Seiberg M. Sebaceous gland regeneration in human skin xenografts. J Invest Dermatol 2010, 130:2131-2133.
29. Pappas A., Anthonavage M., Gordon J.S. Metabolic fate and selective utilization of major fatty acids in human sebaceous gland. J Invest Dermatol 2002, 118:164-171.
30. Theory and pactice of histo-technology 1980, 137-158. Battelle Press. D.C. Sheehan, B.B. Hrapchak (Eds.).
31. Lutsky B.N., Budak M., Koziol P., Monahan M., Neri R.O. The effects of a nonsteroid antiandrogen, flutamide, on sebaceous gland activity. J Invest Dermatol 1975, 64:412-417.
32. Slominski A., Wortsman J., Luger T., Paus R., Solomon S. Corticotropin releasing hormone and proopiomelanocortin involvement in the cutaneous response to stress. Physiol Rev 2000, 80:979-1020.
33. Hoogduijn M.J., McGurk S., Smit N.P., Nibbering P.H., Ancans J., van der Laarse A., et al. Ligand-dependent activation of the melanocortin 5 receptor: cAMP production and ryanodine receptor-dependent elevations of [Ca(2+)](I). Biochem Biophys Res Commun 2002, 290:844-850.
34. Kaufmann R., Mielke V., Reimann J., Klein C.E., Sterry W. Cellular and molecular composition of human skin in long-term xenografts on SCID mice. Exp Dermatol 1993, 2:209-216.
35. Latham J.A., Redfern C.P., Thody A.J., De Kretser T.A. Immunohistochemical markers of human sebaceous gland differentiation. J Histochem Cytochem 1989, 37:729-734.
36. Thiboutot D. Acne: hormonal concepts and therapy. Clin Dermatol 2004, 22:419-428.
37. Chen C., Puy L.A., Simard J., Li X., Singh S.M., Labrie F. Local and systemic reduction by topical finasteride or flutamide of hamster flank organ size and enzyme activity. J Invest Dermatol 1995, 105:678-682.
38. Janiczek-Dolphin N., Cook J., Thiboutot D., Harness J., Clucas A. Can sebum reduction predict acne outcome?. Br J Dermatol 2010, 163:683-688.
39. Downing D.T., Stewart M.E., Wertz P.W., Colton S.W., Strauss J.S. Skin lipids. Comp Biochem Physiol 1983, 76:673-678.
40. Nicolaides N. Skin lipids: their biochemical uniqueness. Science 1974, 186:19-26.
41. Ganceviciene R., Graziene V., Bohm M., Zouboulis C.C. Increased in situ expression of melanocortin-1 receptor in sebaceous glands of lesional skin of patients with acne vulgaris. Exp Dermatol 2007, 16:547-552.
42. Ito K., Sato S., Nishijima A., Hiraga K., Hidano A. Melanogenic melanocytes in human sebaceous glands. Experientia 1976, 32:511-512.
43. Sato S., Hiraga K., Nishijima A., Hidano A. Neonatal sebaceous glands: fine structure of sebaceous and dendritic cells. Acta Derm Venereol 1977, 57:279-287.
44. Robbins L.S., Nadeau J.H., Johnson K.R., Kelly M.A., Roselli-Rehfuss L., Baack E., et al. Pigmentation phenotypes of variant extension locus alleles result from point mutations that alter MSH receptor function. Cell 1993, 72:827-834.
45. Butler A.A., Cone R.D. The melanocortin receptors: lessons from knockout models. Neuropeptides 2002, 36:77-84.
46. Rees J.L. The melanocortin 1 receptor (MC1R): more than just red hair. Pigment Cell Res 2000, 13:135-140.
47. Ganceviciene R., Böhm M., Fimmel S., Zouboulis C.C. The roleof neuropeptides in the multifactorial pathogenesis of Acne vulgaris. Dermatoendocrinology 2009, 1:170-176.
48. Kadekaro A.L., Kanto H., Kavanagh R., Abdel-Malek Z.A. Significance of the melanocortin 1 receptor in regulating human melanocyte pigmentation, proliferation, and survival. Ann N Y Acad Sci 2003, 994:359-365.
49. Abdel-Malek Z.A., Knittel J., Kadekaro A.L., Swope V.B., Starner R. The melanocortin 1 receptor and the UV response of human melanocytes-a shift in paradigm. Photochem Photobiol 2008, 84:501-508.
50. MacNeil D.J., Howard A.D., Guan X., Fong T.M., Nargund R.P., Bednarek M.A., et al. The role of melanocortins in body weight regulation: opportunities for the treatment of obesity. Eur J Pharmacol 2002, 450:93-109.
51. Grieco P., Cai M., Liu L., Mayorov A., Chandler K., Trivedi D., et al. Design and microwave-assisted synthesis of novel macrocyclic peptides active at melanocortin receptors: discovery of potent and selective hMC5R receptor antagonists. J Med Chem 2008, 51:2701-2707.
52. Alexis A.F. Clinical considerations on the use of concomitant therapy in the treatment of acne. J Dermatolog Treat 2008, 19:199-209.
53. Wrobel A., Seltmann H., Fimmel S., Muller-decker K., Tsukada M., Bogdanoff B., et al. Differentiation and apoptosis in human immortalized sebocytes. J Invest Dermatol 2003, 120:175-181.