Inhibition of 5α-reductase activity in SZ95 sebocytes and HaCaT keratinocytes in vitro

Hormone and Metabolic Research

Volumn 39, Issue 2, 2007, Pages 141-148

  Seiffert, K ^a   Seltmann, H ^b   Fritsch, M ^c   Zouboulis, C C ^b,d  

^a MICHIGAN STATE UNIVERSITY   (United States)

^b CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

^c BAYER PHARMA AG   (Germany)

^d DESSAU MEDICAL CENTER   (Germany)

Author keywords

5 reductase inhibitors; Acne; Androgens; Anti androgens; Cell proliferation; Keratinocytes; Sebaceous gland

Indexed keywords

4,7BETA DIMETHYL 4 AZACHOLESTAN 3 ONE; ANDROSTANOLONE; DIHYDROFINASTERIDE; FINASTERIDE; INOCOTERONE ACETATE; SPIRONOLACTONE; STEROID 5ALPHA REDUCTASE; STEROID 5ALPHA REDUCTASE INHIBITOR; TESTOSTERONE; TUROSTERIDE; UNCLASSIFIED DRUG; 4,7BETA-DIMETHYL-4-AZACHOLESTAN-3-ONE; ANDROGEN; ANDROGEN RECEPTOR; AZASTEROID; CHOLESTENONE 5ALPHA REDUCTASE;

ARTICLE; CELL PROLIFERATION; CONTROLLED STUDY; DRUG INHIBITION; ENZYME ACTIVITY; ENZYME INHIBITION; HORMONE METABOLISM; HUMAN; HUMAN CELL; IN VITRO STUDY; KERATINOCYTE; PRIORITY JOURNAL; SKIN DISEASE; CELL CULTURE; DRUG ANTAGONISM; DRUG EFFECT; ENZYMOLOGY; METABOLISM; PROTEIN SYNTHESIS; SEBACEOUS GLAND;

ANDROGENS; AZASTEROIDS; CELL PROLIFERATION; CELLS, CULTURED; CHOLESTENONE 5 ALPHA-REDUCTASE; FINASTERIDE; HUMANS; KERATINOCYTES; PROTEIN BIOSYNTHESIS; RECEPTORS, ANDROGEN; SEBACEOUS GLANDS; TESTOSTERONE;

EID: 34047217292     PISSN: 00185043     EISSN: None     Source Type: Journal    
DOI: 10.1055/s-2007-961814     Document Type: Article

References (36)

1. Chen W, Thiboutot D, Zouboulis CC: Cutaneous androgen metabolism - Basic research and clinical perspectives. J Invest Dermatol 2002; 119: 992-1007
2. Zouboulis CC, Degitz K: Androgen action on human skin - From basic research to clinical significance. Exp Dermatol 2004; 13 (Suppl 4): 5-10
3. Sansone G, Reisner RM: Differential rates of conversion of testosterone to dihydrotestosterone in acne and in normal human skin - a possible pathogenic factor in acne. J Invest Dermatol 1971; 56: 36-72
4. Chen W, Yang C-C, Sheu H-M, Seltmann H, Zouboulis CC: Expression of sex-determining genes in human sebaceous glands and their possible roles in pathogenesis of acne. J Eur Acad Dermatol Venereol , in press
5. Chen W, Tsai S-J, Liao C-Y, Tsai R-Y, Chen Y-R, Pan B-J, Hung C-L, Zouboulis CC: Higher levels of steroidogenic acute regulatory protein and type I 3β-hydroxysteroid dehydrogenase in the scalp of men with androgenetic alopecia. J Invest Dermatol 2006; 126: 2332-2335
6. Thiboutot D, Harris G, Iles V, Cimis G, Guilliland H, Hagari S: Activity of the type 1 5alpha-reductase exhibits regional differences in isolated sebaceous glands and whole skin. J Invest Dermatol 1995; 105: 209-214
7. Chen W, Zouboulis CC, Fritsch M, Blume-Peytavi U, Kodelja V, Goerdt S, Luu-The V, Orfanos CE: Evidence of heterogeneity and quantitative differences of the type 1 5α-reductase expression in cultured human skin cells. Evidence of its presence in melanocytes. J Invest Dermatol 1998; 110: 84-89
8. Luu-The V, Sugimoto Y, Puy L, Labrie Y, Lopez Solache I, Singh M, Labrie F: Characterization, expression and immunohistochemical localization of 5 alpha-reductase in human skin. J Invest Dermatol 1994; 102: 221-226
9. Eicheler W, Dreher M, Hoffmann R, Happle R, Aumüller G: Immunohistochemical evidence for differential distribution of 5 alpha-reductase isoenzymes in human skin. Br J Dermatol 1995; 133: 371-376
10. Bayne EK, Flanagan J, Einstein M, Ayala J, Chang B, Azzolina B, Whiting DA, Mumford RA, Thiboutot D, Singer II, Harris G: Immunohistochemical localization of types 1 and 2 5α-reductase in human scalp. Br J Dermatol 1999; 141: 481-491
11. Thiboutot D, Bayne E, Thorne J, Gilliland K, Flanagan J, Shao Q, Light J, Helm K: Immunolocalization of 5alpha-reductase isozymes in acne lesions and normal skin. Arch Dermatol 2000; 136: 1125-1129
12. Fritsch M, Orfanos CE, Zouboulis CC: Sebocytes are the key regulators of androgen homeostasis in human skin. J Invest Dermatol 2001; 116: 793-800
13. Leyden J, Bergfeld W, Drake L, Dunlap F, Goldman MP, Gottlieb AB, Heffernan MP, Hickman JG, Hordinsky M, Jarrett M, Kang S, Lucky A, Peck G, Phillips T, Rapaport M, Roberts J, Savin R, Sawaya ME, Shalita A, Shavin J, Shaw JC, Stein L, Stewart D, Strauss J, Swinehart J, Swinyer L, Thiboutot D, Washenik K, Weinstein G, Whiting D, Pappas F, Sanchez M, Terranella L, Waldstreicher J: A systemic type 1 5 alpha-reductase inhibitor is ineffective in the treatment of acne vulgaris. J Am Acad Dermatol 2004; 50: 443-447
14. Bowring N: The development of BRL 7660 as an anti-acne agent. Skinmed 2005; 4: 211-213
15. Zouboulis CC, Seltmann H, Neitzel H, Orfanos CE: Establishment and characterization of an immortalized human sebaceous gland cell line (SZ95). J Invest Dermatol 1999; 113: 1011-1020
16. Boukamp P, Petrussevska RT, Breitkreutz D, Hornung J, Markham A, Fusenig NE: Normal keratinization in a spontaneously immortalized aneuploid human keratinocyte cell line. J Cell Biol 1988; 106: 761-778
17. Zouboulis CC, Garbe C, Krasagakis K, Krüger S, Schröder K, Orfanos CE: A fluoremetric rapid microassay to identify anti-proliferative compounds for human melanoma cells in vitro. Melanoma Res 1991; 1: 91-95
18. Thiboutot D, Martin P, Volikos L, Gilliland K: Oxidative activity of the type 2 isozyme of 17beta-hydroxysteroid dehydrogenase (17beta-HSD) predominates in human sebaceous glands. J Invest Dermatol 1998; 111: 390-395
19. Rosenfield RL, Deplewski D, Kentsis A, Ciletti N: Mechanisms of androgen induction of sebocyte differentiation. Dermatology 1998; 196: 43-46
20. Akamatsu H, Zouboulis CC, Orfanos CE: Control of human sebocyte proliferation in vitro by testosterone and 5-alpha-dihydrotestosterone is dependent on the localization of the sebaceous glands. J Invest Dermatol 1992; 99: 509-511
21. Ellsworth K, Azzolina B, Baginsky W, Bull H, Chang B, Cimis G, Mitra S, Toney J, Bakshi RK, Rasmusson CR, Tolman RL, Harris GS: MK386: a potent, selective inhibitor of the human type 1 5alpha-reductase. J Steroid Biochem Mol Biol 1996; 58: 377-384
22. Schwartz JI, Tanaka WK, Wang DZ, Ebel DL, Geissler LA, Dallob A, Hafkin B, Gertz BJ: MK-386, an inhibitor of 5alpha-reductase type 1, reduces dihydrotestosterone concentrations in serum and sebum without affecting dihydrotestosterone concentrations in semen. J Clin Endocrinol Metab 1997; 82: 1373-1377
23. Tian G, Stuart JD, Moss ML, Domanico PL, Bramson HN, Patel IR, Kadwell SH, Overton LK, Kost TA, Mook RA, Jr et al.: 17β-(N-tert- butylcarbomoyl)-4-aza-5α-androstane-1-en-3-one is an active site directed slow time-dependent inhibitor of human steroid 5α-reductase 1. Biochemistry J 1994; 33: 2291-2296
24. Imperato-Mc Ginley J, Gautier T, Cai L-Q, Yee B, Epstein J, Pochi P: The androgen control of sebum production. Studies of subjects with dihydrotestosterone deficiency and complete androgen insensitivity. J Clin Endocrinol Metab 1993; 76: 524-528
25. Dallob AL, Sadick NS, Unger W, Lipert S, Geissler LA, Gregoire SL, Nguyen HH, Moore EC, Tanaka WK: The effect of finasteride a 5α-reductase inhibitor, on scalp skin testosterone and dihydrotestosterone concentration in patients with male pattern baldness. J Clin Endocrinol Metab 1994; 79: 703-706
26. Kaufman KD, Olsen EA, Whiting D, Savin R, De Villez R, Bergfeld W, Price VH, Van Neste D, Roberts JL, Hordinsky M, Shapiro J, Binkowitz B, Gorm ley GJ: Finasteride in the treatment of men with androgenic alopecia. Finasteride male pattern hair loss study group. J Am Acad Dermatol 1998; 39: 578-589
27. Wong IL, Morris RS, Chang L, Spahn MA, Stanczyk FZ, Lobo RA: A prospective randomized trial comparing finasteride to spironolactone in the treatment of hirsute woman. J Clin Endocrinol Metab 1995; 80: 233-238
28. Di Salle E, Guidici D, Briatico G, Ornati G, Panzeri A: Hormonal effects of turosteride, a 5α-reductase inhibitor in the rat. J Steroid Biochem Mol Biol 1993; 46: 549-555
29. Iehle C, Delso S, Guirou O, Tate R, Raynaud JP, Martin PM: Human prostatic steroid 5α-reductase isoforms - a comparative study of selective inhibitors. J Steroid Biochem Molec Biol 1995; 54: 273-279
30. Mowszowicz I, Wright F, Vincens M, Rigaud C, Nahoud K, Mavier P, Guillemant S, Kuttenn F, Mauvais-Jarvis P: Androgen metabolism in hirsute patients treated with cyproterone acetate. J Steroid Biochem 1984; 20: 757-761
31. Corvol P, Michaud A, Menard J, Freifeld M, Mahoudeau J: Antiandrogenic affects of spironolactones: mechanism of action. Endocrinology 1975; 97: 52-58
32. Serafini PC, Catalino J, Lobo RA: The effect of spironolactone on genital skin 5α-reductase activity. J Steroid Biochem 1985; 23: 191-194
33. Bouton MM, Lecaque D, Secchi J, Tournemine C: Effect of a new topically active antiandrogen (RU 38882) on the rat sebaceous gland: comparison with cyproterone acetate. J Invest Dermatol 1986; 86: 163-167
34. Battmann T, Bonfils A, Branche C, Humbert J, Goubet F, Teutsch G, Philibert D: RU 58841, a new specific topical antiandrogen: a candidate of choice for the treatment of acne, androgenetic alopecia and hirsutism. J Steroid Biochem Molec Biol 1994; 48: 55-60
35. Fimmel S, Saborowski A, Térouanne B, Sultan C, Zouboulis CC: Inhibition of the androgen receptor by antisense oligonucleotides regulates the biological activity of androgens in SZ95 sebocytes. Horm Metab Res 2007, in press
36. Zouboulis CC, Eady A, Philpott M, Goldsmith LA, Orfanos C, Cunliffe WJ, Rosenfield R: What is the pathogenesis of acne? Exp Dermatol 2005; 14: 143-152