Analysis of the role of CRH in the regulation of hair cycle using CRH knockout mouse

本研究的目的是阐明皮肤CRH-POMC系统对小鼠毛发周期的调节作用。在2003年，我们证明了心理应激通过CRH的作用延长了毛发周期的端粒期，CRH在毛囊角质形成细胞和皮脂腺细胞中强烈表达。2004年，我们利用CRH基因敲除小鼠和野生小鼠分析了脱毛诱导毛发循环的可能机制。结果表明，在生长期早期，神经生长因子(NGF)在毛囊角质形成细胞、皮脂腺细胞和平滑肌细胞中快速表达和产生。胶质细胞源性神经营养因子(GDNF)、P物质(SP)、促肾上腺皮质激素(ACTH)和黑素细胞刺激素(MSH)在脱毛诱导的毛发周期中也有波动。随后，真皮和脂肪组织中SP阳性神经纤维和活化的肥大细胞数量增多。在两种小鼠模型中，它们的表达和产物没有差异。我们推测，NGF的产生激增以及随后从神经末梢释放的SP在自发毛发循环的诱导和进展中具有重要意义。有一种可能性是，这些亲神经因子刺激皮肤POMC的表达，而不存在CRH。

The objective of the present study is to elucidate the role of the cutaneous CRH-POMC system on the regulation of the murine hair cycle. In the prededing year (2003) we demonstrated that psychological stress prolonged the telogen stage of the hair cycle via the action of CRH which was strongly expressed in follicular keratinocytes and sebaceous gland cells. In the present year (2004) we analyzed the possible mechanism of depilation induced hair cycling using CRH knockout mouse and wild mouse.The result showed that the rapid expression and production of nerve growth factor(NGF) in the early anagen stage (anagen I-III) in follicular keratinocytes, sebaceous gland cells and smooth muscle cells. Glial cell line-derived neutrophic factor(GDNF), substance P(SP), ACTH and melanocyte stimulating hormone(MSH) were also found to fluctuate during the depilation induced hair cycling. Subsequently SP positive nerve fibers and activated mast cells increased in number in the dermis and adipose tissue. There was no difference in their expression and production between both mouse models.We postulate a surge in NGF production and subsequent release of SP from nerve endings are significant in the induction and progression of the spontaneous hair cycling. There is a possibility that these neurotrophilic factors stimulate the expression of cutaneous POMC without the presence of CRH.