SFE2005 Poster Presentations Steroids to include Cushing's (15 abstracts)
Dept Biomedical Sciences, University of Bradford, Bradford, United Kingdom.
Oestrogens can prevent or delay the age-related deterioration of the skin. Post-menopausal women have a reduced rate of wound healing, which can be reversed by oestrogen therapy. However, the mechanisms underlying these effects remain poorly understood. To understand more fully the role of oestrogen in the cutaneous wound healing process we have measured migration, proliferation and the secretion of mitogenic factors by cultured dermal fibroblasts in response to17β-oestradiol.
Primary cultures of dermal fibroblasts were established from female breast skin (n=5, mean age 29.4 yrs, range 27–33yrs) and assayed in serum-free and phenol red-free medium. The effect of 17β-oestradiol (10 nM) on cell migration was evaluated using a scratch-wound assay. Changes in DNA synthesis were determined by measuring 3H-thymidine uptake. Conditioned medium was collected after 24 hours. The mitogenic effect of this medium was assayed on other dermal fibroblasts.
A significant (p<0.05; n=5) increase in the migration of dermal fibroblasts in the scratch-wound assay was seen after 48 hrs with 17β-oestradiol. In addition, wounded cells incubated with 17β-oestradiol also showed a significant (p<0.05, n=5) increase in DNA synthesis. Medium collected from dermal fibroblasts conditioned in the presence of 17β-oestradiol for 24 hrs also had a stimulatory effect on the DNA synthesis of other dermal fibroblasts (n=3).
These results demonstrate that oestrogen has a direct effect on dermal fibroblast proliferation and migration in vitro, which supports the improved wound healing rates seen with oestrogen therapy. Furthermore, 17β-oestradiol appears to stimulate dermal fibroblasts to secrete soluble, paracrine, mitogenic factors. Identification of these factors and the molecular mechanisms involved will help to develop improved therapies for cutaneous wound healing, particularly in the aging population.