Regulation of Postnatal Lung Development and Homeostasis by Estrogen Receptor β

Cesare Patrone, Tobias N. Cassel, Katarina Pettersson, Yun Shang Piao, Guojun Cheng, Paolo Ciana, Adriana Maggi, Margaret Warner, Jan Åke Gustafsson, Magnus Nord

Research output: Contribution to journalArticle

154 Scopus citations

Abstract

Estrogens have well-documented effects on lung development and physiology. However, the classical estrogen receptor α (ERα) is undetectable in the lung, and this has left many unanswered questions about the mechanism of estrogen action in this organ. Here we show, both in vivo and in vitro, that ERβ is abundantly expressed and biologically active in the lung. Comparisons of lungs from wild-type mice and mice with an inactivated ERβ gene (ERβ-/-) revealed decreased numbers of alveoli in adult female ERβ-/- mice and findings suggesting deficient alveolar formation as well as evidence of surfactant accumulation. Platelet-derived growth factor A (PDGF-A) and granulocyte-macrophage colony-stimulating factor (GM-CSF), key regulators of alveolar formation and surfactant homeostasis, respectively, were decreased in lungs of adult female ERβ-/- mice, and direct transcriptional regulation of these genes by ERβ was demonstrated. This suggests that estrogens act via ERβ in the lung to modify PDGF-A and GM-CSF expression. These results provide a potential molecular mechanism for the gender differences in alveolar structure observed in the adult lung and establish ERβ as a previously unknown regulator of postnatal lung development and homeostasis.

Original languageEnglish (US)
Pages (from-to)8542-8552
Number of pages11
JournalMolecular and Cellular Biology
Volume23
Issue number23
DOIs
StatePublished - Dec 2003

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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