TY - JOUR
T1 - Regulation of Postnatal Lung Development and Homeostasis by Estrogen Receptor β
AU - Patrone, Cesare
AU - Cassel, Tobias N.
AU - Pettersson, Katarina
AU - Piao, Yun Shang
AU - Cheng, Guojun
AU - Ciana, Paolo
AU - Maggi, Adriana
AU - Warner, Margaret
AU - Gustafsson, Jan Åke
AU - Nord, Magnus
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2003/12
Y1 - 2003/12
N2 - 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.
AB - 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.
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U2 - 10.1128/MCB.23.23.8542-8552.2003
DO - 10.1128/MCB.23.23.8542-8552.2003
M3 - Article
C2 - 14612399
AN - SCOPUS:0344013638
SN - 0270-7306
VL - 23
SP - 8542
EP - 8552
JO - Molecular and Cellular Biology
JF - Molecular and Cellular Biology
IS - 23
ER -