Kang S, Li X Y, Voorhees J J
Department of Dermatology, University of Michigan Medical Center, Ann Arbor, 48109-0314, USA.
J Investig Dermatol Symp Proc. 1996 Apr;1(1):15-21.
All-trans retinoic acid and 1,25-dihydroxyvitamin D3 are biologically active hormones derived from metabolism of vitamins A and D, respectively. Their cellular effects in physiology and pharmacology are mediated mainly through their nuclear receptors, retinoic acid receptors (RARs), and vitamin D receptor (VDR), which are members of the steroid/thyroid hormone receptor superfamily. The nuclear receptor superfamily is a group of hormone (ligand)-dependent transcription factors that bind to specific DNA recognition sequences located in the promotor region of target genes and modulate the gene transcription. Both RARs and VDR bind to DNA in the form of heterodimers with retinoid X receptor (RXR) as the key partner. In human skin epidermis, endogenous RAR and VDR bind to their respective enhancer elements as heterodimers (RAR-RXR, VDR-RXR) and not as homodimers. 9-cis retinoic acid is the natural ligand for RXRs. Because RXR heterodimerizes with either RARs or VDR, it functions as a key protein in the overall retinoid or vitamin D response of a given biological system. The contribution of RXRs in coregulating these signaling pathways is likely to depend on the abundance of the RXRs within target cells, the relative amounts of other receptors with which they can dimerize, and the availability of their ligands (hormones). Understanding each of these components in human skin in vivo will lead to practical applications in dermatologic therapeutics.
全反式维甲酸和1,25 - 二羟基维生素D3分别是维生素A和维生素D代谢产生的生物活性激素。它们在生理学和药理学上的细胞效应主要通过其核受体介导，即维甲酸受体（RARs）和维生素D受体（VDR），它们是类固醇/甲状腺激素受体超家族的成员。核受体超家族是一组激素（配体）依赖性转录因子，它们与位于靶基因启动子区域的特定DNA识别序列结合并调节基因转录。RARs和VDR均以与视黄酸X受体（RXR）作为关键伙伴的异二聚体形式与DNA结合。在人类皮肤表皮中，内源性RAR和VDR以异二聚体（RAR - RXR、VDR - RXR）而非同二聚体的形式与其各自的增强子元件结合。9 - 顺式维甲酸是RXRs的天然配体。由于RXR与RARs或VDR形成异二聚体，它在给定生物系统的整体类视黄醇或维生素D反应中起关键作用。RXRs在共同调节这些信号通路中的作用可能取决于靶细胞内RXRs的丰度、与之形成二聚体的其他受体的相对量以及其配体（激素）的可用性。了解体内人类皮肤中的这些成分将有助于皮肤科治疗的实际应用。
