Department of Dermatology, University of Lübeck, D-23538 Lübeck, Germany.
Br J Dermatol. 2013 Jul;169(1):146-51. doi: 10.1111/bjd.12264.
Hair and epithelial keratins constitute the major structural components of the skin and its appendages, including the hair fibre. While it is appreciated that selected steroid hormones regulate specific keratins, little is known about the neuroendocrine control of human hair keratin expression. Preliminary evidence had suggested that thyrotropin-releasing hormone (TRH) may regulate keratin gene transcription.
To clarify whether TRH operates as a novel neuroendocrine regulator of human hair and epithelial keratin expression under physiologically relevant conditions in situ.
Microdissected human female scalp hair follicles (HFs) and female scalp skin were treated in serum-free organ culture for 12 h to 6 days with 100 ng mL(-1) TRH or vehicle. Both quantitative immunohistomorphometry and quantitative real-time polymerase chain reaction were utilized to assess expression of selected keratins.
TRH significantly increased expression of the hair keratins K31 and K32, while that of K85 and K86, and of the epithelial keratins K14 and K17, was reduced. In the interfollicular epidermis, TRH stimulated expression of K6, K14 and K17, both at the mRNA and protein levels. Stimulation of the same keratins was also evident in the eccrine sweat and sebaceous glands.
Selected human hair and epithelial keratins are modulated in situ. This may be relevant to explain hair shaft growth-promoting effects of TRH. Our pilot study suggests that the neuroendocrine controls that regulate the expression of human keratins deserve more systematic exploration and that these may be harnessed therapeutically.
毛发和上皮角蛋白构成了皮肤及其附属物(包括毛发纤维)的主要结构成分。虽然人们已经认识到某些类固醇激素可以调节特定的角蛋白,但对于神经内分泌对人类角蛋白表达的控制却知之甚少。初步证据表明,促甲状腺素释放激素(TRH)可能调节角蛋白基因的转录。
阐明在生理相关条件下,TRH 是否作为一种新的神经内分泌调节剂来调节人头发和上皮角蛋白的表达。
将女性头皮毛囊(HFs)和头皮皮肤进行微切割,在无血清器官培养中分别用 100ng/ml 的 TRH 或载体处理 12 小时至 6 天。采用定量免疫组织形态计量学和实时定量聚合酶链反应来评估选定角蛋白的表达。
TRH 显著增加了 K31 和 K32 等毛发角蛋白的表达,而 K85 和 K86 以及 K14 和 K17 等上皮角蛋白的表达则减少。在毛囊间表皮中,TRH 刺激 K6、K14 和 K17 的 mRNA 和蛋白水平表达。在汗腺和皮脂腺中也观察到相同的角蛋白的刺激作用。
选择的人类毛发和上皮角蛋白在原位受到调节。这可能与 TRH 促进毛干生长的作用有关。我们的初步研究表明,调节人类角蛋白表达的神经内分泌控制值得更系统地探索,并且这些控制可能具有治疗潜力。