The Effect of Dehydroepiandrosterone on Expression of Elastin in Cultured Skin Fibroblasts

Kim, Chang Duk; Ryoo, Young Wook; Lee, Kyu Suk

Abstract

BACKGROUND: Dehydroepiandrosterone(DHEA) and its sulfate ester dehydro- epiandrosterone sulfate(DHEA-S) are the steroids secreted most abdundantly by the human adrenal gland, but the physiologic role remains uncertain. Elastin is one of the major extracellular matrix components of the dermis and plays an important role in providing elasticity and resilience of the skin. Expression of elastin genes at transcriptional level is regulated and modulated by cytokines, vitamin D3, insulin-like growth factor-1, and steroids. But only little is known about the molecular and cellular mechanism underlying the effect of DHEA on the expression of elastin in cultured skin fibroblasts.
OBJECTIVE
The purpose of this study was to examine the effect of DHEA on elastin gene expression in cultured skin fibroblasts.
METHODS
In this study, the effects of DHEA were examined by Northern blot hybridization, chloramphenicol acetyltransferase assay(CAT), and laser scanning microscopy in cultured human fibroblasts.
RESULTS
In Northern blot hybridization, levels of elastin mRNA were increased 1.5-fold at 1 nmol of DHEA, 4.2-fold at 0.1 mol and 6.5-fold at 10 mol, compared to untreated control. DHEA caused a alteration in the elastin mRNA expression in a dose-related fashion. In CAT assay, the relative mRNA CAT activity was 0.9 at a concentration of 1 nmol, 2.4 at 0.1 mol, and 2.7 at a 10 mol. DHEA caused a marked increase on elastin promotor activity. In confocal laser scanning microscopy, the immunosignal for elastin in DHEA-treated fibroblasts is more intense compared to the control.
CONCLUSION
These results indicate that DHEA may be a powerful up-regulator of elastin production, suggesting transcriptional activation of gene expression in cultured skin fibroblasts.