The human sebocyte culture model provides new insights into development and management of seborrhoea and acne

Christos C. Zouboulis, L. Xia, H. Akamatsu, H. Seltmann, M. Fritsch, S. Hornemann, R. Rühl, W. Chen, H. Nau, C. E. Orfanos

研究成果: ジャーナルへの寄稿学術論文査読

194 被引用数 (Scopus)

抄録

Seborrhoea and acne are exclusively human diseases and sebaceous gland differentiation is species specific. Therefore, fundamental research on human sebaceous cell function and control requires human in vitro models. The human sebocyte culture model, introduced in 1989, has been used in several studies to elucidate sebaceous gland activity and its regulation at the cellular level. Cultured human sebocytes have been shown to preserve important sebocytic characteristics, although they undergo an incomplete terminal differentiation in vitro. In vitro synthesis of free fatty acids without bacterial involvement and marked interleukin la expression at the mRNA and protein levels with no further induction by lipopolysaccharides lead to the assumption that human sebocytes may initiate acne lesions by an intrinsic mechanism. Androgens affected sebocyte activity in vitro in a manner dependent on the localization of the sebaceous glands. In vitro stimulation of sebocyte proliferation by androgens could be completely abolished by spironolactone. Cultured sebocytes strongly expressed type 1 5α-reductase and metabolized testosterone to androstenedione, 5α-androstanedione, 5α-dihydrotestosterone, androsterone and 5α-androstanediol, whereas the levels of 5α-reductase activity were probably not feedback regulated. 4,7β-Dimethyl-4-aza-5α-cholestan-3-one, a type 1 5α-reductase inhibitor, induced an early, marked down-regulation of 5α-reductase activity in human sebocytes in vitro, while hydrofinasteride, a type 2 inhibitor, required 103-fold higher concentrations to induce similar effects. Stimulation of sebocyte proliferation by insulin, thyroid-stimulating hormone and hydrocortisone indicates that the hormonal control of the sebaceous gland could be a complex mechanism. Retinoids inhibited sebocyte proliferation in a dose-dependent manner and down-regulated lipid synthesis and sebocyte differentiation in vitro. Isotretinoin was the most potent compound. On the other hand, vitamin A was found essential for sebocyte activity and differentiation in vitro and could be partially substituted by synthetic retinoids. The inhibitory effect of isotretinoin on sebocyte proliferation was barely affected by the presence of vitamin A. The low persistent isotretinoin levels or, more likely, the considerably elevated tretinoin concentrations detected in human sebocytes after treatment with isotretinoin in vitro may be responsible for the inhibitory effect of this compound on sebocyte activity.

本文言語英語
ページ(範囲)21-31
ページ数11
ジャーナルDermatology
196
1
DOI
出版ステータス出版済み - 1998
外部発表はい

All Science Journal Classification (ASJC) codes

  • 皮膚病学

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