Kono M, Nagata H, Umemura S, Kawana S, Osamura R Y
Department of Dermatology, Nippon Medical School, Tokyo, Japan.
FASEB J. 2001 Oct;15(12):2297-9. doi: 10.1096/fj.01-0254fje. Epub 2001 Aug 17.
Systemic stresses induce corticotropin-releasing hormone (CRH) expression in hypothalamus. CRH is released to the pituitary gland, where it stimulates proopiomelanocortin (POMC) production acting via the CRH receptor (CRH-R). CRH and POMC peptides are also detected in sites outside of the central nervous system (CNS), such as the skin. However, it has not been elucidated whether these peptides detected in the skin are derived from CNS or are produced locally. Using immunohistochemical and in situ reverse-transcription (RT)-PCR techniques, we demonstrated coexpression of CRH and POMC mRNAs in the epidermis and pilosebaceous units of the human skin. This coexpression was confirmed by the combination of laser-capture microdissection (LCM) with RT-PCR, analyzing mRNA expressions in captured sebaceous cells. Immunoreactivities and expressions of CRH and POMC mRNAs were strong in inflammatory lesions, melanocytic nevus, seborrheic keratosis, and also in the periphery of the benign tumor. These findings suggest that CRH and POMC peptides are produced locally in the skin and are regulated by inflammatory cells as well as by autocrine mechanisms. The skin may have "a local stress response system," whose activity is mediated by CRH and POMC peptides, in an equivalent to hypothalamus-pituitary adrenal axis.
全身性应激可诱导下丘脑促肾上腺皮质激素释放激素（CRH）的表达。CRH释放至垂体，在垂体中它通过CRH受体（CRH-R）刺激阿黑皮素原（POMC）的产生。在中枢神经系统（CNS）以外的部位，如皮肤中也可检测到CRH和POMC肽。然而，皮肤中检测到的这些肽是否源自CNS或在局部产生尚未阐明。利用免疫组织化学和原位逆转录（RT）-PCR技术，我们证明了CRH和POMC mRNA在人皮肤的表皮和毛囊皮脂腺单位中共表达。通过激光捕获显微切割（LCM）与RT-PCR相结合，分析捕获的皮脂腺细胞中的mRNA表达，证实了这种共表达。CRH和POMC mRNA的免疫反应性和表达在炎症性病变、黑素细胞痣、脂溢性角化病以及良性肿瘤周边均较强。这些发现表明，CRH和POMC肽在皮肤中局部产生，并受炎症细胞以及自分泌机制的调节。皮肤可能具有“局部应激反应系统”，其活性由CRH和POMC肽介导，相当于下丘脑-垂体-肾上腺轴。
