A Role for Estrogen Receptor-α and Estrogen Receptor-β in Collagen Biosynthesis in Mouse Skin

Abstract

Hormonal regulation of the dermal collagenous extracellular matrix plays a key role in maintaining proper tissue homeostasis, however the factors and pathways involved in this process are not fully defined. This study investigated the role of estrogen receptors (ERs) in the regulation of collagen biosynthesis in mice lacking ERα or ERβ. Collagen content was significantly increased in the skin of ΕRα-/- mice as measured by acetic acid extraction and the hydroxyproline assay and correlated with the decreased levels of MMP-15 and elevated collagen production by ΕRα-/- fibroblasts. In contrast, collagen content was decreased in the skin of ERβ-/- mice despite markedly increased collagen production by ERβ-/- fibroblasts. However, expression of several matrix metalloproteinases (MMPs), including MMP-8 and -15 was significantly elevated suggesting increased degradation of dermal collagen. Furthermore, ERβ-/- mice were characterized by significantly reduced levels of small leucine proteoglycans (SLRPs), lumican and decorin, leading to the defects in collagen fibrillogenesis and possibly less stable collagen fibrils. ERα-/- mice also exhibited fibrils with irregular structure and size, which correlated with increased levels of lumican and decorin. Together, these results demonstrate distinct functions of estrogen receptors in the regulation of collagen biosynthesis in mouse skin in vivo.

Glycosaminoglycan and proteoglycan in skin aging

“…In ovariectomized mice, dermal thickness and decorin expression were found to be reduced [45]. Estrogen receptor ß knockout mice showed similarly reduced dermal thickness and decorin expression; however, estrogen receptor α knockout mice showed increased dermal thickness and collagen and decorin expression, indicating dominant regulation of dermal ECM production by estrogen receptor ß [46]. In contrast, in gonadectomized mice, dermal thickness and collagen expression were reduced, while decorin remained unchanged [45].…”

Mind the Gap: Sex Bias in Basic Skin Research

“…In cutaneous biology, comparative studies are beginning todefine the distinct action of estrogen on estrogen alpha and beta receptors and their relationships with the IGF-1 receptor in understanding wound re-epithelialization, macrophage polarization, and why skin wound healing is slower in men than in women (Campbell et al, 2010; Emmerson et al, 2012, 2013; Markiewicz et al, 2013; Campbell et al, 2014). The impact of estrogen on keratinocyte differentiation and cutaneous SCC progression in mice (Brooks et al, 2014), as well as the lower catalase levels in the skin and ultraviolet B-induced myeloid cells of male mice (Sullivan et al, 2012) may contribute to the two- to threefold increase in nonmelanoma skin cancers in men and the larger, histologically advanced, more numerous, and less inflamed UVB-induced SCCs in male hairless mice (Thomas-Ahner et al, 2007).…”

S-Equol, an Antioxidant Metabolite of Soy Daidzein, and Oxidative Stress in Aging

“…Markiewicz et al 22 assessed the role of skin estrogen receptors in ERα and ERβ knockout, aged female mice. The importance of ERβ in mediating the protective effect of estrogen against photoaging has been demonstrated by Markiewicz et al 22 using mice lacking ERα or ERβ, and by Chang et al 23 with estrogen receptor selective compounds.…”