Slominski A, Wortsman J, Luger T, Paus R, Solomon S
Department of Pathology, Loyola University Medical Center, Maywood, Illinois, USA.
Physiol Rev. 2000 Jul;80(3):979-1020. doi: 10.1152/physrev.2000.80.3.979.
The skin is a known target organ for the proopiomelanocortin (POMC)-derived neuropeptides alpha-melanocyte stimulating hormone (alpha-MSH), beta-endorphin, and ACTH and also a source of these peptides. Skin expression levels of the POMC gene and POMC/corticotropin releasing hormone (CRH) peptides are not static but are determined by such factors as the physiological changes associated with hair cycle (highest in anagen phase), ultraviolet radiation (UVR) exposure, immune cytokine release, or the presence of cutaneous pathology. Among the cytokines, the proinflammatory interleukin-1 produces important upregulation of cutaneous levels of POMC mRNA, POMC peptides, and MSH receptors; UVR also stimulates expression of all the components of the CRH/POMC system including expression of the corresponding receptors. Molecular characterization of the cutaneous POMC gene shows mRNA forms similar to those found in the pituitary, which are expressed together with shorter variants. The receptors for POMC peptides expressed in the skin are functional and include MC1, MC5 and mu-opiate, although most predominant are those of the MC1 class recognizing MSH and ACTH. Receptors for CRH are also present in the skin. Because expression of, for example, the MC1 receptor is stimulated in a similar dose-dependent manner by UVR, cytokines, MSH peptides or melanin precursors, actions of the ligand peptides represent a stochastic (predictable) nonspecific response to environmental/endogenous stresses. The powerful effects of POMC peptides and probably CRH on the skin pigmentary, immune, and adnexal systems are consistent with stress-neutralizing activity addressed at maintaining skin integrity to restrict disruptions of internal homeostasis. Hence, cutaneous expression of the CRH/POMC system is highly organized, encoding mediators and receptors similar to the hypothalamic-pituitary-adrenal (HPA) axis. This CRH/POMC skin system appears to generate a function analogous to the HPA axis, that in the skin is expressed as a highly localized response which neutralizes noxious stimuli and attendant immune reactions.
皮肤是源自阿片-促黑素细胞皮质素原（POMC）的神经肽α-黑素细胞刺激素（α-MSH）、β-内啡肽和促肾上腺皮质激素（ACTH）的已知靶器官，也是这些肽的来源。POMC基因以及POMC/促肾上腺皮质激素释放激素（CRH）肽的皮肤表达水平并非一成不变，而是由诸如与毛发周期相关的生理变化（生长期最高）、紫外线辐射（UVR）暴露、免疫细胞因子释放或皮肤病理状况等因素决定。在细胞因子中，促炎白细胞介素-1可使皮肤中POMC mRNA、POMC肽和MSH受体水平显著上调；UVR也能刺激CRH/POMC系统的所有组分表达，包括相应受体的表达。皮肤POMC基因的分子特征显示，其mRNA形式与垂体中的相似，且与较短的变体共同表达。皮肤中表达的POMC肽受体具有功能，包括MC1、MC5和μ-阿片受体，不过最主要的是识别MSH和ACTH的MC1类受体。CRH受体也存在于皮肤中。例如，由于UVR、细胞因子、MSH肽或黑色素前体以类似的剂量依赖性方式刺激MC1受体表达，配体肽的作用代表了对环境/内源性应激的随机（可预测）非特异性反应。POMC肽以及可能还有CRH对皮肤色素、免疫和附属器系统的强大作用，与旨在维持皮肤完整性以限制内环境稳态破坏的应激中和活性相一致。因此，CRH/POMC系统的皮肤表达高度有序，编码与下丘脑-垂体-肾上腺（HPA）轴相似的介质和受体。这种CRH/POMC皮肤系统似乎产生了一种类似于HPA轴的功能，在皮肤中表现为高度局部化的反应，可中和有害刺激及随之而来的免疫反应。
