Quevedo M E, Slominski A, Pinto W, Wei E, Wortsman J
Department of Pathology, Loyola University Medical Center, Maywood, Illinois 60153, USA.
In Vitro Cell Dev Biol Anim. 2001 Jan;37(1):50-4. doi: 10.1290/1071-2690(2001)037<0050:peocrh>2.0.co;2.
The hypothalamic-pituitary-adrenal (HPA) axis is the major stress response system. Several components of the HPA axis, such as corticotropin-releasing hormone (CRH) and POMC peptides and their receptors are also present in the skin. In earlier studies, we showed that CRH inhibits cellular proliferation of immortalized human keratinocytes. We now examine further the functional activity of the HPA axis in the skin, by characterizing the actions of CRH on normal foreskin keratinocytes. The CRH receptor was detected as CRH-R1 antigen at 47 kDa in the cultured keratinocytes by Western blotting, and immunohistochemistry demonstrated its presence in the epidermal and follicular keratinocytes. CRH is also biologically active in cultured keratinocytes, where it inhibits proliferation and enhances the interferon-gamma-stimulated expression of the hCAM and ICAM-1 adhesion molecules and of the HLA-DR antigen. These effects were concentration-dependent, with maximal activity at CRH 10(-7) M. Thus, in the keratinocyte, the most important cellular component of the epidermis, CRH appears to induce a shift in energy metabolism away from proliferation activity, and toward the enhancement of immunoactivity. Therefore, similar to its central actions, cutaneous CRH may also he involved in the stress response, but at a highly localized level.
下丘脑-垂体-肾上腺（HPA）轴是主要的应激反应系统。HPA轴的几个组成部分，如促肾上腺皮质激素释放激素（CRH）、阿黑皮素原肽及其受体也存在于皮肤中。在早期研究中，我们发现CRH可抑制永生化人角质形成细胞的细胞增殖。现在，我们通过描述CRH对正常包皮角质形成细胞的作用，进一步研究HPA轴在皮肤中的功能活性。通过蛋白质印迹法在培养的角质形成细胞中检测到CRH受体为47 kDa的CRH-R1抗原，免疫组织化学显示其存在于表皮和毛囊角质形成细胞中。CRH在培养的角质形成细胞中也具有生物活性，它可抑制细胞增殖，并增强干扰素-γ刺激的hCAM和ICAM-1黏附分子以及HLA-DR抗原的表达。这些作用呈浓度依赖性，在CRH 10(-7) M时活性最大。因此，在角质形成细胞（表皮最重要的细胞成分）中，CRH似乎诱导能量代谢从增殖活动转向免疫活性增强。因此，与它在中枢的作用类似，皮肤中的CRH可能也参与应激反应，但作用水平高度局限。
