The Johnson & Johnson Skin Research Center, Consumer Product Worldwide, a Unit of Johnson & Johnson Consumer Companies, Inc. 199 Grandview Rd., Skillman, NJ 08558, USA.
J Dermatol Sci. 2011 Jul;63(1):23-32. doi: 10.1016/j.jdermsci.2011.04.001. Epub 2011 Apr 15.
The melanocortin receptor-5 (MC5R) is present in human sebaceous glands, where it is expressed in differentiated sebocytes only. The targeted disruption of MC5R in mice resulted in reduced sebaceous lipid production and a severe defect in water repulsion.
To investigate the physiological function of MC5R in human sebaceous glands.
A novel MC1R and MC5R antagonist (JNJ-10229570) was used to treat primary human sebaceous cells or human skins grafted onto severe combined immunodeficient (SCID) mice. Transcription profiling, lipid analyses, and histological and immunohistochemical staining were used to analyze the effect of MC5R inhibition on sebaceous gland differentiation and sebum production.
JNJ-10229570 dose dependently inhibited the production of sebaceous lipids in cultured primary human sebocytes. Topical treatment with JNJ-10229570 of human skins transplanted onto SCID mice resulted in a marked decrease in sebum-specific lipid production, sebaceous gland's size and the expression of the sebaceous differentiation marker epithelial-membrane antigen (EMA). Treatment with flutamide, a known inhibitor of sebum production, gave similar results, validating the human skin/SCID mouse experimental system for sebaceous secretion studies.
Our data suggest that antagonists of MC1R and MC5R could be effective sebum suppressive agents and might have a potential for the treatment of acne and other sebaceous gland pathologies.
黑素皮质素受体-5（MC5R）存在于人类的皮脂腺中，仅在分化的皮脂腺细胞中表达。MC5R 在小鼠中的靶向缺失导致皮脂脂质产生减少和水驱避严重缺陷。
研究 MC5R 在人类皮脂腺中的生理功能。
使用一种新型的 MC1R 和 MC5R 拮抗剂（JNJ-10229570）处理原代人皮脂腺细胞或移植到严重联合免疫缺陷（SCID）小鼠的人皮肤。转录谱分析、脂质分析以及组织学和免疫组织化学染色用于分析 MC5R 抑制对皮脂腺分化和皮脂产生的影响。
JNJ-10229570 剂量依赖性地抑制培养的原代人皮脂腺细胞中皮脂脂质的产生。将 JNJ-10229570 局部应用于移植到 SCID 小鼠的人皮肤上，导致皮脂特异性脂质产生、皮脂腺大小和皮脂分化标志物上皮膜抗原（EMA）的表达明显减少。使用氟他胺（一种已知的皮脂产生抑制剂）进行治疗也得到了类似的结果，验证了人皮肤/ SCID 小鼠实验系统在皮脂分泌研究中的有效性。
我们的数据表明，MC1R 和 MC5R 的拮抗剂可能是有效的皮脂抑制剂，并且可能具有治疗痤疮和其他皮脂腺疾病的潜力。
