title: 17β-estradiol replacement reverses age-related lung disease in estrogen-deficient C57BL/6J mice.
abstract: The role that estrogens play in the aging lung is poorly understood. Remodeling of the aging lung with thickening of the alveolar walls and reduction in the number of peripheral airways is well recognized. The present study was designed to address whether estrogen deficiency would affect age-associated changes in the lungs of female C57BL/6J mice. Lungs isolated from old mice (24 months old, estrogen-deficient) demonstrated decreased lung volume and decreased alveolar surface area. There was no difference in alveolar number in the lungs of old and young mice (6 months old, estrogen-replete). Estrogen replacement restored lung volume, alveolar surface area, and alveolar wall thickness to that of a young mouse. Estrogen receptor-α (ERα) protein expression increased without a change in ERβ protein expression in the lung tissue isolated from old mice. In the lungs of old mice, the number of apoptotic cells was increased as well as the activation of matrix metalloproteinase-2 and ERK. Young mice had the highest serum 17β-estradiol levels that decreased with age. Our data suggest that in the aging female mouse lung, estrogen deficiency and an increase of ERα expression lead to the development of an emphysematous phenotype. Estrogen replacement partially prevents these age-associated changes in the lung architecture by restoration of interalveolar septa. Understanding the role of estrogens in the remodeling of the lung during aging may facilitate interventions and therapies for aging-related lung disease in women.
authors.affiliation: Departments of Pulmonary and Critical Care Medicine (M.K.G., R.C., S.S., M.A.) and Surgery (X.X., S.J.E.) and the Diabetes Research Institute (V.M.), University of Miami Miller School of Medicine, Miami, Florida 33137; and Department for Lung Development and Remodeling (P.R., R.V.), Max-Planck-Institute for Heart and Lung Research, 61231 Bad Nauheim, Germany.
authors.forename: Marilyn K
authors.initials: MK
authors.lastname: Glassberg
authors.forename: Rhea
authors.initials: R
authors.lastname: Choi
authors.forename: Vita
authors.initials: V
authors.lastname: Manzoli
authors.forename: Shahriar
authors.initials: S
authors.lastname: Shahzeidi
authors.forename: Peter
authors.initials: P
authors.lastname: Rauschkolb
authors.forename: Robert
authors.initials: R
authors.lastname: Voswinckel
authors.forename: Muddassir
authors.initials: M
authors.lastname: Aliniazee
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Xia
authors.forename: Sharon J
authors.initials: SJ
authors.lastname: Elliot
mesh_terms: D000375:Aging / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology / Q000627:therapeutic use*; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D015914:Estrogen Replacement Therapy; D005260:Female; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008171:Lung Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D047628:Estrogen Receptor alpha; D012333:RNA, Messenger; D004958:Estradiol; D020778:Matrix Metalloproteinase 2