Carlberg C, Saurat J H
Clinique de Dermatologie, Hôpital Cantonal Universitaire, Geneva, Switzerland.
J Investig Dermatol Symp Proc. 1996 Apr;1(1):82-6.
The molecular structure of the biological active form of vitamin D, 1 alpha,25-dihydroxyvitamin D3 (VD), and the vitamin A derivatives all-trans and 9-cis retinoic acid (RA) are not related. The nuclear receptors for VD (VDR) and retinoids (RAR and RXR), however, are members of the same superfamily of ligand-activated transcription factors. We observed stable VDR-RXR and VDR-RAR heterodimers in solution and their transcriptional activity on different types of response elements. Both heterodimeric complexes are activated by VD, but, depending on the relative expression of the nuclear receptors, retinoids can have either co-stimulating or repressing effects. This demonstrates that VD and retinoid signaling are linked at the level of gene regulation and may explain the similar effects of both hormones on cell proliferation and differentiation. This concept may be applied for treating skin diseases, with the hope that a synergism will be observed, allowing better responses with lower doses of each compound. Preliminary observations suggest that psoriasis, cutaneous T-cell lymphomas, and actinic keratoses might be potential targets for VD-retinoid associations.
维生素D的生物活性形式1α,25 - 二羟基维生素D3（VD）的分子结构与维生素A衍生物全反式和9 - 顺式视黄酸（RA）并无关联。然而，VD的核受体（VDR）和类视黄醇的核受体（RAR和RXR）属于同一配体激活转录因子超家族的成员。我们在溶液中观察到了稳定的VDR - RXR和VDR - RAR异二聚体及其对不同类型反应元件的转录活性。两种异二聚体复合物均被VD激活，但根据核受体的相对表达情况，类视黄醇可能具有共刺激或抑制作用。这表明VD和类视黄醇信号传导在基因调控水平上相互关联，并且可能解释了这两种激素对细胞增殖和分化的相似作用。这一概念可应用于治疗皮肤疾病，有望观察到协同作用，从而使每种化合物以更低剂量就能产生更好的疗效。初步观察表明，银屑病、皮肤T细胞淋巴瘤和光化性角化病可能是VD - 类视黄醇联合治疗的潜在靶点。
