Induction of Collagen by Estradiol

Abstract

To evaluate the effectiveness of topical estradiol in stimulating collagen I and III production in naturally aged and photoaged human skin of postmenopausal women and age-matched men.Design: Vehicle-controlled treatment followed by biochemical and immunohistochemical analyses of skin biopsy specimens.Setting: Academic referral center.Participants: Seventy healthy volunteers (40 postmenopausal women with a mean age of 75 years, and 30 men with a mean age of 75 years) with photodamaged skin.Interventions: Topical application of estradiol, 0.01%, 0.1%, 1%, or 2.5% or vehicle on aged or photoaged skin, with biopsy specimens taken after last treatment.Main Outcome Measures: De novo synthesis of collagen by quantitative polymerase chain reaction, immunohistochemistry, and enzyme-linked immunosorbent assay.Results: Topical estradiol increased procollagen I and III messenger RNA and collagen I protein levels in sun-protected aged hip skin in postmenopausal women and, to a lesser extent, in age-matched men. Surprisingly, no significant changes in production were observed in women or men after 2-week estradiol treatment of photoaged forearm or face skin, despite similar expression of estrogen receptors (ER-␣, ER-␤, and GPR30) in aged and photoaged skin. Estradiol treatment induced the estrogenresponsive gene GREB1, indicating that penetration of topical estradiol and genomic response to estrogen were similar in the 3 anatomic sites.Conclusions: Two-week topical estradiol treatment stimulates collagen production in sun-protected hip skin, but not in photoaged forearm or face skin, in postmenopausal women and aged-matched men. These findings suggest that menopause-associated estrogen decline is involved in reduced collagen production in sun-protected skin. Interestingly, alterations induced by long-term sun exposure hinder the ability of topical 2-week estradiol to stimulate collagen production in aged skin.

Fli1 Is a Negative Regulator of Estrogen Receptor α in Dermal Fibroblasts

“…As according to a recent study ERα represents a predominant isoform expressed in human dermal fibroblasts (Rittie et al ., 2008), we focused on this isoform and first confirmed its expression by reverse transcription-PCR (RT-PCR) (Figure 1a) and western blot (Figure 1b). MCF-7 breast cancer cells, which express full-length ERα, as well as 46 and 36 kDa splice variants (Flouriot et al ., 2000; Wang et al ., 2005), were used as a positive control.…”

“…In this study we observed upregulation of ERα in response to TGF-β, suggesting that signaling through this receptor might be involved in the downstream effects of TGF-β, including ECM production in dermal fibroblasts. However, in spite of a large number of studies documenting stimulatory effects of topical estrogen on collagen accumulation in the skin (Rittie et al ., 2008), the mechanistic aspects of collagen gene regulation by estrogen remain poorly understood. Estrogen was also shown to induce collagen and other matrix proteins in cultured dermal fibroblasts (Surazynski et al ., 2003; Soldano et al ., 2010).…”

“…It increases skin thickness and collagen content (Varila et al ., 1995; Rittie et al ., 2008), decreases fine wrinkles (Creidi et al ., 1994), accelerates wound healing (Ashcroft et al ., 1999), and changes the quality of scarring (Ashcroft et al ., 1997). Estrogen exerts its actions through the well-characterized estrogen receptors (ERs), ERα and ERβ; however, their specific roles in the skin have not been fully defined.…”

Reduced cell cohesiveness of outgrowths from eccrine sweat glands delays wound closure in elderly skin

“…IHC was performed as previously described (Rittié et al ., 2008), and slides were mounted with 90% glycerin or ProLong Gold medium (both from Thermo Fisher Scientific, Waltham, MA, USA). Imaging of horizontally cut sections was performed with a Leica MXFL III Stereo Microscope (Leica Microsystems, Buffalo Grove, IL, USA; accessed at the Microscopy and Image‐Analysis Laboratory, Biomedical Research Core Facilities, University of Michigan Medical School).…”

Stem Cell Aging: Mechanisms, Consequences, Rejuvenation

“…In particular in females in postmenopausal age, the blood concentrations of estrogen and progesterone drop considerably, and this is accompanied by the typical features of skin aging, i.e., dryness, epidermal atrophy, diminution of collagen, loss of elasticity, wrinkle formation, and impaired wound healing (Bolognia et al 1989 ;Brincat 2000 ;Rittie et al 2008 ;Sumino et al 2004 ). In particular in females in postmenopausal age, the blood concentrations of estrogen and progesterone drop considerably, and this is accompanied by the typical features of skin aging, i.e., dryness, epidermal atrophy, diminution of collagen, loss of elasticity, wrinkle formation, and impaired wound healing (Bolognia et al 1989 ;Brincat 2000 ;Rittie et al 2008 ;Sumino et al 2004 ).…”