Ovarian hormone deficiency and wound healing

Wound Repair Regeneration

Taylor

Meskiri

et al. 2008

Improved wound healing of hairy skin may involve mesenchymal hair follicle cells with stem cell potential and enhancement by estrogen therapy. How estrogen affects follicular dermal papilla (DP) and dermal sheath (DS) cells in wound healing is unknown. Therefore, a comparison of estradiol action on DP, DS, and corresponding interfollicular dermal fibroblasts (DF) in a scratchwound assay was performed using matching primary cultures established from female temporo-occipital scalp. All three cell types expressed mRNA transcripts and protein for estrogen receptors a (ERa) and b (ERb). DF ERa transcripts were half that of DP and one-third of DS cells, while DF ERb transcripts were two-thirds of DP and DS cells. In the scratch-wound assay all three cells types migrated at similar rates, but only the rate of DF was enhanced by estradiol. Mechanical wounding increased DNA synthesis rates of all three cell types and increased the secretion of collagen by DF and DS cells. All three secreted similar basal levels of vascular endothelial growth factor (VEGF), which was increased by wounding DF and DS cells, but not DP cells. DP cells required estradiol to increase VEGF secretion; by contrast VEGF secretion was decreased by estradiol in wounded DS cells. These results highlight differences in the responses of DF, DP, and DS cells to estradiol in a scratch-wound assay, providing further support for the dichotomy of cellular functions in the hair follicle. Further understanding of the role of estrogen in cutaneous wound healing may have important implications for the management of chronic wounds and scarring.Skin appendages play a key role in epithelial regeneration following cutaneous wounding. Specifically, the regenerative properties of the adult hair follicle suggest that hair follicle stem cells may play an important role in the wound healing process. While epidermal stem cells of the hair follicle allow for re-epithelialization, 1 the hair follicle mesenchyme, namely the dermal papilla (DP) and dermal sheath (DS), may play a part in dermal repair following cutaneous wounding. 2The importance of the hair follicle in cutaneous wound healing is provided by animal models. For example, full-thickness wounds heal more quickly in hairy animals than in humans, with greater contraction and less scar formation. Furthermore, a relationship between wound healing and the hair cycle has been demonstrated, with skin containing anagen (growing) follicles healing more rapidly. In humans, it has also been suggested that cutaneous wounds heal better in hair-bearing skin. When used for split-thickness skin grafting, rapid donor site healing has been reported in scalp skin with low infection rates and minimal scar formation.3 Furthermore, in a prospective study it was shown that following split-thickness skin graft harvesting, donor sites on hair-bearing scalp skin heal significantly better than those on nonhairy thigh skin. 4 Evidence for the stem cell potential of both DP and DS cells comes from a study demonstrating that cells der...

mentioning

confidence: 99%

Differing responses of human follicular and nonfollicular scalp cells in an in vitro wound healing assay: Effects of estrogen on vascular endothelial growth factor secretion

Wound Repair Regeneration

Taylor

Meskiri

et al. 2008

“…Ageing is associated with impaired wound healing and problematic chronic wounds. Although oestradiol and dehydroepiandrosterone (DHEA) improve wound healing (1–4), levels fall with age. Two intracellular receptors (ERα and ERβ) bind 17β‐oestradiol with similar affinity (5).…”

Section: Introductionmentioning

confidence: 99%

Effects of oestrogen agonists on human dermal fibroblasts in an in vitro wounding assay

Experimental Dermatology

Sharpe

Thornton

2009

Oestrogen and dehydroepiandrosterone (DHEA) improve wound healing, but circulating levels decline significantly with age. Recently, the selective oestrogen receptor modulators (SERMs) tamoxifen and raloxifene have been shown to improve age-associated impaired wound healing. Therefore, we have evaluated the effects of 17b-oestradiol, ERa and ERb agonists, tamoxifen, raloxifene and DHEA on human dermal fibroblasts using an in vitro wound assay. An ERa agonist, 17b-oestradiol and DHEA all significantly accelerated cell migration; the DHEA effect was blocked with an aromatase inhibitor. Tamoxifen, raloxifene and DHEA all significantly increased DNA synthesis; the DHEA stimulatory effect was reversed by an aromatase inhibitor. This study demonstrates that 17b-oestradiol, an ERa agonist, tamoxifen, raloxifene and DHEA (following conversion to oestrogen) all have significant effects on human fibroblasts, the key mesenchymal cell involved in the wound healing process. Further understanding of the mechanisms involved may have important implications for the management of age-related impaired wound healing.Key words: DHEA -oestrogen -raloxifene -SERMs -tamoxifen Please cite this paper as: Effects of oestrogen agonists on human dermal fibroblasts in an in vitro wounding assay. Experimental Dermatology 2009; 18: 988-990.

17β-Estradiol regulates the secretion of TGF-β by cultured human dermal fibroblasts

Journal of Biomaterials Science, Polymer Edition

Nelson

Sharpe

et al. 2008

Estrogen plays an important role in skin homeostasis, as demonstrated by the changes seen in the skin of post-menopausal women, changes reversed by HRT. Estrogen also has a role in wound healing, since estrogen deficiency as occurs post-menopausally and in ovariectomised animals, is associated with a reduced rate of wound healing. Estrogen appears to modulate all phases of wound healing with effects on inflammatory cells, epithelialization, angiogenesis, extracellular matrix deposition and tissue remodelling. This study was designed to investigate the effects of 17beta-estradiol on cultured human dermal fibroblasts using an in vitro wound-healing assay. The end points investigated were cell migration, proliferation, total collagen secretion and active TGF-beta1 secretion. 17beta-estradiol significantly increased the migration and proliferation of cultured dermal fibroblasts following mechanical wounding, although the secretion of total soluble collagen was not altered. An increase in TGF-beta1 was demonstrated by unwounded confluent dermal fibroblast monolayers in response to 17beta-estradiol, but paradoxically, a decrease in the secretion of TGF-beta1 was demonstrated in the mechanically wounded dermal fibroblasts. These results identify human dermal fibroblasts as estrogen target cells and provide further evidence for a role by which estrogen regulates this particular cell type as part of the wound-healing process. However, the paradoxical nature of the effect of estrogen on TGF-beta1 secretion following mechanical wounding suggests that the cellular mechanism of action is complex. A greater understanding of the cell-specific action of estrogen may help to develop therapies that will improve cutaneous wound healing in the future.