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

Abstract

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.

Estrogens and aging skin

“…Estrogen stimulates the migration of cultured human dermal fibroblasts derived from scalp, 43 breast, 44 and abdominal skin 45 . Interestingly, increased migration occurred only in response to 17β-estradiol and an ERα agonist, while an ERβ agonist had no effect 45 .…”

Toll-Like Receptor 4 Expression in Human Breast Implant Capsules

“…6,25,26 17β-Estradiol increases the production of TGF-β and fibronectin, which are among the main stimuli involved in myofibroblast differentiation and contraction. 27,28 The main receptors for this hormone are estrogen receptor-α and estrogen receptor-β. In a murine model of cutaneous scarring, estrogen receptor-α stimulation induced conversion of fibroblasts into myofibroblasts, whereas estrogen receptor-β activation resulted in extracellular matrix production and increased wound tensile strength.…”

Intracrine sex steroid synthesis and signaling in human epidermal keratinocytes and dermal fibroblasts

“…Previous dose-response assays using this technique have shown that a range of concentrations of 17b-estradiol (10 27 -10 29 M) and DHEA (10 25 -10 28 M) all stimulated cell migration to a similar level (37,39). The ability of the cells to metabolize these steroids was determined by including 100 nM Arimidex (to block aromatase activity) in the presence and absence of DHEA or testosterone, and 100 nM STX64 (to block STS activity) in the presence and absence of DHEA-S. Migration was quantitated as previously described (28,30).…”

“…Migration was measured at 4,8,12,24, and 48 h in triplicate dishes for each donor. Conditioned medium, collected from dermal fibroblast cultures 24 h after scratching as previously described (37), was also assessed for its effect on the migration of epidermal keratinocytes.…”