A Role for Estrogen Receptor-alpha and Estrogen Receptor-beta in Collagen Biosynthesis in Mouse Skin

Hormonal regulation of the dermal collagenous extracellular matrix has 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 either ER alpha or ER beta. Collagen content was significantly increased in the skin of ER alpha(-/-) mice, as measured by acetic acid extraction and the hydroxyproline assay, and correlated with the decreased levels of matrix nnetalloproteinase (MMP)-15 and elevated collagen production by ER alpha(-/-) fibroblasts. In contrast, collagen content was decreased in the skin of ER beta(-/-) mice, despite markedly increased collagen production by ER beta(-/-) fibroblasts. However, expression of several MMPs, including MMP-8 and -15, was significantly elevated, suggesting increased degradation of dermal collagen. Furthermore, ER beta(-/-) mice were characterized by significantly reduced levels of small leucine proteoglycans, lumican (Lum), and decorin (Dcn), leading to defects in collagen fibrillogenesis and possibly less stable collagen fibrils. ER alpha(-/-) mice also exhibited fibrils with irregular structure and size, which correlated with increased levels of Lum and Dcn. Together, these results demonstrate distinct functions of ERs in the regulation of collagen biosynthesis in mouse skin in vivo. Journal of Investigative Dermatology (2013) 133, 120-127; doi:10.1038/jid.2012.264; published online 16 August 2012