Calvo E, Luu-The V, Morissette J, Martel C, Labrie C, Bernard B, Bernerd F, Deloche C, Chaussade V, Leclaire J, Labrie F
Oncology and Molecular Endocrinology Research Center, Centre de recherche du Centre hospitalier de l'Université Laval (CHUL Research Center), Québec City, Quebec, G1V 4G2 Canada.
J Steroid Biochem Mol Biol. 2008 Dec;112(4-5):186-93. doi: 10.1016/j.jsbmb.2008.10.008. Epub 2008 Nov 1.
The objective of this study was to explore, for the first time, the changes in the pangenomic profile induced in human skin in women treated with dehydroepiandrosterone (DHEA) applied locally. Sixty postmenopausal women participated in this phase II prospective, randomized, double-blind and placebo-controlled study. Women were randomized to the twice daily local application of 0% (placebo), 0.3%, 1% or 2% DHEA cream. Changes in the pangenomic expression profile were studied using Affymetrix Genechips. Significant changes (p<0.05) in sixty-six DHEA-responsive probe sets corresponding to 52 well-characterized genes and 9 unknown gene sequences were identified. A dose-dependent increase in the expression of several members of the collagen family was observed, namely COL1, COL3 and COL5 as well as the concomitant modulation of SPARC, a gene required for the normal deposition and maturation of collagen fibrils in the dermis. Several genes involved in the proliferation and differentiation of keratinocytes were also modulated. In addition, topical DHEA reduced the expression of genes associated with the terminal differentiation and cornification of keratinocytes. Our results strongly suggest the possibility that DHEA could exert an anti-aging effect in the skin through stimulation of collagen biosynthesis, improved structural organization of the dermis while modulating keratinocyte metabolism.
本研究的目的是首次探索局部应用脱氢表雄酮（DHEA）治疗的女性皮肤中泛基因组图谱的变化。60名绝经后女性参与了这项II期前瞻性、随机、双盲和安慰剂对照研究。女性被随机分为每日两次局部应用0%（安慰剂）、0.3%、1%或2%DHEA乳膏。使用Affymetrix基因芯片研究泛基因组表达谱的变化。在对应于52个特征明确的基因和9个未知基因序列的66个DHEA反应探针集中发现了显著变化（p<0.05）。观察到胶原蛋白家族几个成员的表达呈剂量依赖性增加，即COL1、COL3和COL5，以及伴随的SPARC调节，SPARC是真皮中胶原纤维正常沉积和成熟所需的基因。几个参与角质形成细胞增殖和分化的基因也受到调节。此外，局部应用DHEA降低了与角质形成细胞终末分化和角质化相关的基因表达。我们的结果强烈表明，DHEA可能通过刺激胶原蛋白生物合成、改善真皮结构组织同时调节角质形成细胞代谢，从而在皮肤中发挥抗衰老作用。
