Pérez Paloma
Instituto de Biomedicina de Valencia; Consejo Superior de Investigaciones Científicas (IBV-CSIC); Valencia, Spain.
Dermatoendocrinol. 2011 Jul;3(3):166-74. doi: 10.4161/derm.3.3.15332. Epub 2011 Jul 1.
Glucocorticoids (GCs) exert their biological and therapeutical actions through the GC receptor (GR), a ligand-dependent transcription factor. Synthetic GC derivatives are widely prescribed for treating numerous cutaneous inflammatory and immune diseases due to their great efficacy. However, chronic treatment with GCs produces adverse side-effects including skin atrophy, delayed wound healing, and in certain cases, GC resistance. The mechanisms underlying the therapeutic actions of the GR in skin have been extensively studied; in contrast, the role of GR as a modulator of epidermal development and homeostasis has received less attention. The ubiquitous functional inactivation of GR results in defective epidermal formation although the underlying mechanisms have not been fully characterized. The use of transcriptomic approaches both in vitro and in vivo allowed the identification of genes that are regulated by GR in developing and adult skin. A main goal to understand the role of GR in skin biology is to identify primary transcriptional targets as well as the signaling pathways mediating GR action. Furthermore, it will be important to decipher the contribution of GR in the different cellular compartments of the skin, including keratinocytes of the interfollicular epidermis and hair follicles, and their respective stem cell progenitors. Additionally, recent findings indicating that the skin acts as a true peripheral endocrine organ implies greater complexity than originally thought. The local production of GCs and other steroid hormones should be considered as a modulator of skin function under homeostatic and diseased conditions. Finally, studying GR function in skin should take into account that the mineralocorticoid receptor may also mediate GC actions and/or regulate transcription either by itself or in combination with GR. Addressing these issues should help to elucidate the mechanisms by which Gr contributes to establishment of a competent epidermal barrier and may also have implications in the context of dermatological treatments based on GC-analogs.
糖皮质激素（GCs）通过糖皮质激素受体（GR）发挥其生物学和治疗作用，GR是一种配体依赖性转录因子。合成GC衍生物因其显著疗效而被广泛用于治疗多种皮肤炎症和免疫疾病。然而，长期使用GC会产生不良副作用，包括皮肤萎缩、伤口愈合延迟，在某些情况下还会导致GC抵抗。GR在皮肤中的治疗作用机制已得到广泛研究；相比之下，GR作为表皮发育和稳态调节剂的作用受到的关注较少。尽管其潜在机制尚未完全明确，但GR的普遍功能失活会导致表皮形成缺陷。在体外和体内使用转录组学方法能够鉴定出在发育中和成年皮肤中受GR调控的基因。理解GR在皮肤生物学中的作用的一个主要目标是确定主要转录靶点以及介导GR作用的信号通路。此外，解读GR在皮肤不同细胞区室中的作用也很重要，这些区室包括毛囊间表皮和毛囊的角质形成细胞及其各自的干细胞祖细胞。此外，最近的研究结果表明皮肤是一个真正的外周内分泌器官，这意味着其复杂性比最初认为的更高。在稳态和疾病状态下，GC和其他类固醇激素的局部产生应被视为皮肤功能的调节剂。最后，研究皮肤中的GR功能时应考虑到盐皮质激素受体也可能介导GC作用和/或单独或与GR结合调节转录。解决这些问题有助于阐明GR对建立健全表皮屏障的作用机制，也可能对基于GC类似物的皮肤病治疗产生影响。
