A role for estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ) in collagen biosynthesis in mouse skin

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.