Modulation of Collagen Metabolism by the Topical Application of Dehydroepiandrosterone to Human Skin

Abstract

Dehydroepiandrosterone (DHEA) and its sulfate conjugate (DHEA-S) are the most abundantly produced human adrenal steroids to be reduced with age. DHEA may be related to the process of skin aging through the regulation and degradation of extracelluar matrix protein. In this study, we demonstrate that DHEA can increase procollagen synthesis and inhibit collagen degradation by decreasing matrix metalloproteinases (MMP)-1 synthesis and increasing tisuue inhibitor of matrix metalloprotease (TIMP-1) production in cultured dermal fibroblasts. DHEA was found to inhibit ultraviolet (UV)-induced MMP-1 production and the UV-induced decrease of procollagen synthesis, probably due to the inhibition of UV-induced AP-1 activity. DHEA (5%) in ethanol:olive oil (1:2) was topically applied to buttock skin of volunteers 12 times over 4 weeks, and was found to significantly increase the expression of procollagen alpha1(I) mRNA and protein in both aged and young skin. On the other hand, topical DHEA significantly decreased the basal expression of MMP-1 mRNA and protein, but increased the expression of TIMP-1 protein in aged skin. We also found that DHEA induced the expressions of transforming growth factor-beta1 and connective tissue growth factor mRNA in cultured fibroblasts and aged skin, which may play a role in the DHEA-induced changes of procollagen and MMP-1 expression. Our results suggest the possibility of using DHEA as an anti-skin aging agent.

An update on the role of the sebaceous gland in the pathogenesis of acne

“…22 Consequently, several researchers have suggested the use of DHEA as an anti-aging agent. 42,43 However, in in vitro experiments DHEA has been shown to have no direct effect on the biological activity of human sebocytes. Substitution with DHEA in elderly persons is accompanied by a small increase of testosterone and estradiol, which may indeed yield an explanation of the clinical change demonstrated 22 suggesting that the action of DHEA may be implemented through indirect pathways.…”

Nuclear import of hTERT requires a bipartite nuclear localization signal mediated by Akt phosphorylation

“…The human osteosarcoma cell line Saos-2 was maintained in McCoy's 5A medium containing 15% fetal bovine serum in 5% CO 2 at 37˚C. Primary cultures of human fibroblasts were established from adult foreskin in DMEM supplemented with 10% fetal calf serum as described elsewhere (Shin et al, 2005).…”

Skin and brain age together: The role of hormones in the ageing process

“…Dehydroepiandrosterone (DHEA) seems to play a key role in the synthesis of extracellular matrix and its decline with age may lead to a decrease in procollagen synthesis and enhancement of collagen degradation by increasing matrix metalloproteinases (MMP)-1 and collagenase synthesis whilsts decreasing tissue inhibitor of matrix metalloprotease (TIMP)-1 and stromelysin-1 production (Lee et al, 2000;Shin et al, 2005). In a double-blind, placebocontrolled study conducted with 280 elderly healthy individuals, 50 mg DHEA was given orally daily over one year.…”