Kauser Sobia, Slominski Andrzej, Wei Edward T, Tobin Desmond J
Department of Biomedical Sciences, University of Bradford, Bradford, West Yorkshire, BD7 1DP, UK.
FASEB J. 2006 May;20(7):882-95. doi: 10.1096/fj.05-5257com.
Human skin is a local source of corticotropin-releasing hormone (CRH) and expresses CRH and CRH receptors (CRH-R) at mRNA and protein levels. Epidermal melanocytes respond to CRH by induction of cAMP with up-regulation of pro-opiomelanocortin gene expression and subsequent production of adrenocorticotropin hormone. However, the role of CRH/CRH-R in melanocyte biology is complicated by the significant heterogeneity of cutaneous melanocyte subpopulations, from continuously active and UV-responsive melanocytes in epidermis to UV nonresponsive, hair growth cycle-coupled melanogenesis in hair follicles. In the present study we report that normal human scalp hair follicle melanocytes express CRH at the mRNA level. Furthermore, CRH, urocortin and CRH-R 1 and 2 were differentially expressed in follicular melanocytes, fibroblasts, and keratinocytes depending on anatomic location and differentiation status in situ and in vitro. Stimulation of follicular melanocytes with CRH and CRH peptides, modified for selectivity for CRH-R1 and/or CRH-R2, variably induced cell melanogenesis, dendricity, and proliferation. CRH-peptides also stimulated the expression and activity of Tyrosinase, and expression of Tyrosinase-related protein-1 and-2. However, a modified urocortin peptide highly selective for CRH-R2 down-regulated melanocyte differentiation phenotype. This study indicates that CRH peptides can differentially influence hair follicle melanocyte behavior not only via CRH-R1 signaling but also by complex cross-talk between CRH-R1 and CRH-R2.
人类皮肤是促肾上腺皮质激素释放激素（CRH）的局部来源，在mRNA和蛋白质水平表达CRH及其受体（CRH-R）。表皮黑素细胞通过诱导cAMP对CRH作出反应，同时上调阿黑皮素原基因表达并随后产生促肾上腺皮质激素。然而，CRH/CRH-R在黑素细胞生物学中的作用因皮肤黑素细胞亚群的显著异质性而变得复杂，从表皮中持续活跃且对紫外线有反应的黑素细胞到毛囊中对紫外线无反应、与毛发生长周期相关的黑素生成。在本研究中，我们报告正常人头皮毛囊黑素细胞在mRNA水平表达CRH。此外，CRH、尿皮质素以及CRH-R 1和2在毛囊黑素细胞、成纤维细胞和角质形成细胞中的表达因解剖位置以及原位和体外的分化状态而异。用针对CRH-R1和/或CRH-R2的选择性修饰的CRH和CRH肽刺激毛囊黑素细胞，可不同程度地诱导细胞黑素生成、树突形成和增殖。CRH肽还刺激酪氨酸酶的表达和活性，以及酪氨酸酶相关蛋白-1和-2的表达。然而，一种对CRH-R2具有高度选择性的修饰尿皮质素肽下调了黑素细胞分化表型。这项研究表明，CRH肽不仅可以通过CRH-R1信号通路，还可以通过CRH-R1和CRH-R2之间复杂的相互作用来不同程度地影响毛囊黑素细胞的行为。
