Testosterone metabolism to 5?-dihydrotestosterone and synthesis of sebaceous lipids is regulated by the peroxisome proliferator-activated receptor ligand linoleic acid in human sebocytes
Abstract
BACKGROUND: Despite the clinical evidence that androgens stimulate sebaceous lipids, androgens in vitro have shown no similar effects. This contradiction led to the assumption that cofactors may be required for lipid regulation and peroxisome proliferator-activated receptor (PPAR) ligands were suggested to be adequate candidates. OBJECTIVES: The influence of testosterone and linoleic acid, a PPAR ligand, as single agents and in combination with of LY191704, a 5alpha-reductase type I inhibitor, was examined on 5alpha-dihydrotestosterone (5alpha-DHT) synthesis and lipid content in human SZ95 sebocytes. METHODS: Cell proliferation and viability were measured by the 4-methylumbelliferyl heptanoate fluorescence assay and by the Boehringer Lactate Dehydrogenase Assay kit, respectively. 5alpha-DHT enzyme-linked immunosorbent assay was used for the detection of 5alpha-DHT synthesis in cell supernatants after treatment, whereas lipid production was documented by means of the Nile red lipid microassay and fluorescence microscopy. RESULTS: Testosterone promoted 5alpha-DHT synthesis (P < 0.001), whereas linoleic acid increased sebaceous lipids (P < 0.001). The combination of testosterone and linoleic acid exhibited a synergistic effect on the synthesis of 5alpha-DHT (P < 0.01 vs. testosterone) and sebaceous lipids (P < 0.01 vs. linoleic acid). Furthermore, LY191704 reduced 5alpha-DHT and sebaceous lipid levels (P < 0.01 and P < 0.001 in comparison with testosterone/linoleic acid, respectively). Cell proliferation and viability remained unchanged under treatment with all compounds tested. CONCLUSIONS: These data suggest a catalytic effect of PPAR ligands on cellular testosterone activation by 5alpha-reduction and the importance of the latter for the regulation of sebaceous lipids.
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Synergy between testosterone or DHT and the PPAR ligand linoleic acid increases lipogenesis.
“while their synergistic effect with the PPAR ligand linoleic acid resulted in increased lipogenesis [200].”
From Steroidogenesis in the skin: Implications for local immune functions (2013) · cites this paper as [200]
Cites
Kliewer, S. A., FORMAN, B. M., Blumberg, B., Ong, E. S., Borgmeyer, U., Mangelsdorf, D. J., Umesono, K., & Evans, R. M. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.15.7355 · Cited by 1,400 · see citing works
Selective Retention of Dihydrotestosterone by Prostatic Nuclei
Anderson, K. M., & Liao, S. (1968) · Nature · doi:10.1038/219277a0 · Cited by 529 · see citing works
Establishment and Characterization of an Immortalized Human Sebaceous Gland Cell Line (SZ95)1
Zouboulis, C. C., Seltmann, H., Orfanos, C. E., & Neitzel, H. (1999) · Journal of Investigative Dermatology · doi:10.1046/j.1523-1747.1999.00771.x · Cited by 363 · see citing works
Self-citationWhat is the pathogenesis of acne?
Zouboulis, C. C., Eady, E. A., Philpott, M., Goldsmith, L. A., Orfanos, C. E., Cunliffe, W. C., & Rosenfield, R. L. (2005) · Experimental Dermatology · doi:10.1111/j.0906-6705.2005.0285a.x · Cited by 340 · see citing works
Self-citationSansone, G., & Reisner, R. M. (1971) · Journal of Investigative Dermatology · doi:10.1111/1523-1747.ep12261252 · Cited by 300 · see citing works
Corticotropin-releasing hormone: An autocrine hormone that promotes lipogenesis in human sebocytes
Zouboulis, C. C., Seltmann, H., Hiroi, N., Chen, W., Young, M., Oeff, M., Scherbaum, W. A., Orfanos, C. E., McCann, S. M., & Bornstein, S. R. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.102180999 · Cited by 290 · see citing works
Self-citationKligman, A. M. (1974) · Journal of Investigative Dermatology · doi:10.1111/1523-1747.ep12676801 · Cited by 277 · see citing works
Alestas, T., Ganceviciene, R., Fimmel, S., Müller-Decker, K., & Zouboulis, C. C. (2006) · Journal of Molecular Medicine · doi:10.1007/s00109-005-0715-8 · Cited by 269 · see citing works
Self-citationSebocytes are the key regulators of androgen homeostasis in human skin
Fritsch, M., Orfanos, C. E., & Zouboulis, C. C. (2001) · Journal of Investigative Dermatology · doi:10.1046/j.1523-1747.2001.01312.x · Cited by 232 · see citing works
Self-citationGiltay, E. J., & Gooren, L. J. G. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.85.8.6710 · Cited by 226 · see citing works
Androgen action on human skin – from basic research to clinical significance
Zouboulis, C. C., & Degitz, K. (2004) · Experimental Dermatology · doi:10.1111/j.1600-0625.2004.00255.x · Cited by 183 · see citing works
Self-citationChen, W., Yang, C.-C., Sheu, H.-M., Seltmann, H., & Zouboulis, C. C. (2003) · Journal of Investigative Dermatology · doi:10.1046/j.1523-1747.2003.12411.x · Cited by 157 · see citing works
Self-citationMechanisms of Androgen Induction of Sebocyte Differentiation
Rosenfield, R. L., Deplewski, D., Kentsis, A., & Ciletti, N. (1998) · Dermatology · doi:10.1159/000017864 · Cited by 156 · see citing works
Akamatsu, H., Zouboulis, C. C., & Orfanos, C. E. (1992) · Journal of Investigative Dermatology · doi:10.1111/1523-1747.ep12616181 · Cited by 135 · see citing works
Self-citationPochi, P. E., & Strauss, J. S. (1969) · Journal of Investigative Dermatology · doi:10.1038/jid.1969.4 · Cited by 120 · see citing works
Orfanos, C. E., Adler, Y. D., & Zouboulis, C. C. (2000) · Hormone Research in Paediatrics · doi:10.1159/000053267 · Cited by 92 · see citing works
Self-citationLY191704: a selective, nonsteroidal inhibitor of human steroid 5 alpha-reductase type 1.
Hirsch, K. S., Jones, C. D., Audia, J. E., Andersson, S., McQuaid, L. A., Stamm, N. B., Neubauer, B. L., Pennington, P., Toomey, R. E., & Russell, D. W. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.11.5277 · Cited by 63 · see citing works
A systemic type i 5 α-reductase inhibitor is ineffective in the treatment of acne vulgaris
Leyden, J., Bergfeld, W., Drake, L., Dunlap, F., Goldman, M. P., Gottlieb, A. B., Heffernan, M. P., Hickman, J. G., Hordinsky, M., Jarrett, M., et al. (2004) · Journal of the American Academy of Dermatology · doi:10.1016/j.jaad.2003.07.021 · Cited by 48 · see citing works
Zouboulis, C. C., Garbe, C., Krasagakis, K., et al. (1991) · Melanoma Research · doi:10.1097/00008390-199106000-00003 · Cited by 37 · see citing works
Self-citationGiltay, E. J. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.85.8.2913 · Cited by 32 · see citing works
Chen, W., Zouboulis, C. C., Fritsch, M., Kodelja, V., & Orfanos, C. E. (1998) · Dermatology · doi:10.1159/000017866 · Cited by 16 · see citing works
Self-citationFimmel, S., Saborowski, A., Orfanos, C. E., et al. (2000) · Hormone Research in Paediatrics · doi:10.1159/000053277 · Cited by 15 · see citing works
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New developments in our understanding of acne pathogenesis and treatment
Kurokawa, I., Danby, F. W., Ju, Q., Wang, X., Xiang, L. F., Xia, L., Chen, W., Nagy, I., Picardo, M., Suh, D. H., et al. (2009) · Experimental Dermatology · doi:10.1111/j.1600-0625.2009.00890.x · Cited by 584 · see citing works
Self-citationSteroidogenesis in the skin: Implications for local immune functions
Slominski, A., Zbytek, B., Nikolakis, G., Manna, P. R., Skobowiat, C., Zmijewski, M., Li, W., Janjetovic, Z., Postlethwaite, A., Zouboulis, C. C., et al. (2013) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2013.02.006 · Cited by 369 · see citing works
Self-citationZouboulis, C., Chen, W.-C., Thornton, M., Qin, K., & Rosenfield, R. (2007) · Hormone and Metabolic Research · doi:10.1055/s-2007-961807 · Cited by 379 · see citing works
Self-citationCannabidiol exerts sebostatic and antiinflammatory effects on human sebocytes
Oláh, A., Tóth, B. I., Borbíró, I., Sugawara, K., Szöllõsi, A. G., Czifra, G., Pál, B., Ambrus, L., Kloepper, J., Camera, E., et al. (2014) · Journal of Clinical Investigation · doi:10.1172/jci64628 · Cited by 268 · see citing works
Self-citationGender differences in skin: A review of the literature
Dao, H., & Kazin, R. A. (2007) · Gender Medicine · doi:10.1016/s1550-8579(07)80061-1 · Cited by 199 · see citing works
Hormones and the pilosebaceous unit
Chen, W.-C., & Zouboulis, C. C. (2009) · Dermato-Endocrinology · doi:10.4161/derm.1.2.8354 · Cited by 110 · see citing works
Self-citationSebum lipids influence macrophage polarization and activation
Lovászi, M., Mattii, M., Eyerich, K., Gácsi, A., Csányi, E., Kovács, D., Rühl, R., Szegedi, A., Kemény, L., Ståhle, M., et al. (2017) · British Journal of Dermatology · doi:10.1111/bjd.15754 · Cited by 88 · see citing works
Self-citationSkin steroidogenesis in health and disease
Nikolakis, G., Stratakis, C. A., Kanaki, T., Slominski, A., & Zouboulis, C. C. (2016) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-016-9390-z · Cited by 76 · see citing works
Self-citationPhuong, C., & Maibach, H. I. (2017) · Textbook of Aging Skin · doi:10.1007/978-3-662-47398-6_93 · Cited by 16 · see citing works
- Authors
- Makrantonaki, E., & Zouboulis, C. C.
- Affiliations
- Stiftung Charité (DE)
- Städtisches Klinikum Dessau (DE)
- Corresponding author
- Zouboulis, C.C.
- Venue
- British Journal of Dermatology
- Publisher
- Oxford University Press (OUP)
- Published
- 2007-03
- Volume
- 156
- Issue
- 3
- Pages
- 428-432
- ISSN
- 0007-0963 (ISSN-L)
- 1365-2133
- OpenAlex
- W2032483892
- Cited by
- 117
- References
- 22
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 5 · 2023: 6 · 2022: 8 · 2021: 6 · 2020: 4 · 2019: 7 · 2017: 4 · 2016: 7 · 2015: 4 · 2014: 14 · 2013: 3 · 2012: 6
- FWCI
- 9.13
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- British Journal of Dermatology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Dermatology › Acne and Rosacea Treatments and Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
- Keywords
- testosterone metabolism, dihydrotestosterone, sebaceous lipids, linoleic acid, peroxisome proliferator-activated receptors, sebocytes, synergistic effect, cell proliferation
- MeSH terms
- Androstanols, Cells, Cultured, Drug Synergism, Humans, Ligands, Lipids, Sebaceous Glands, Testosterone, 17-Ketosteroids, Quinolones, Linoleic Acid, Peroxisome Proliferator-Activated Receptors, Cell Proliferation, 5-alpha Reductase Inhibitors
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