title: Estrogen deficiency promotes cigarette smoke-induced changes in the extracellular matrix in the lungs of aging female mice.
abstract: Female smokers have a faster decline in lung function with increasing age and overall develop a greater loss of lung function than male smokers. This raises the question of whether estrogen status in women affects susceptibility to cigarette smoke (CS)-induced lung disease. Mouse models suggest that female mice are more susceptible than males to CS-induced lung disease. Moreover, young CS-exposed female mice develop emphysema earlier than male mice. The purpose of this study was to characterize the relationship of estrogen status on the pattern and severity of CS-induced lung disease. In this study, 15-month-old female C57BL/6J mice were ovariectomized and administered either placebo (pla) or 17β-estradiol (E2, 0.025 mg) 2 weeks after ovariectomy. They were further divided into those that were exposed to CS and no-smoke controls (NSC). Mice were exposed to CS in stainless steel inhalation chambers 3 hours a day, 5 days a week for 6 months, and sacrificed after 24 weeks of CS exposure. Blood and urine were collected at sacrifice to measure estrogen and cotinine levels, a metabolite of nicotine. Uterine weight was recorded as an indicator of estrogen status. Results showed that CS in the absence of E2induced a decrease in hydroxyproline content, macrophage number, and respiratory chain complex-1 protein. CS without E2also resulted in an increase in matrix metalloproteinase-2 activity and apoptosis and a change in the ratio of estrogen receptor subtype. These findings were abrogated with administration of E2,suggesting that estrogen deficiency increases susceptibility to CS-induced lung disease.
authors: Department of Medicine, Miller School of Medicine, University of Miami, Miami, Fla; Department of Surgery, Miller School of Medicine, University of Miami, Miami, Fla. Electronic address: mglassbe@med.miami.edu.
authors: Marilyn K
authors: MK
authors: Glassberg
authors: Department of Surgery, Miller School of Medicine, University of Miami, Miami, Fla.
authors: Paola
authors: P
authors: Catanuto
authors: Division of Pediatric Pulmonology, Department of Pediatrics, Miller School of Medicine, University of Miami, Miami, Fla.
authors: Shahriar
authors: S
authors: Shahzeidi
authors: Henry County Hospital, New Castle, Ind.
authors: Muddassir
authors: M
authors: Aliniazee
authors: Department of Medicine, Miller School of Medicine, University of Miami, Miami, Fla.
authors: Sarit
authors: S
authors: Lilo
authors: Department of Surgery, Miller School of Medicine, University of Miami, Miami, Fla.
authors: Gustavo A
authors: GA
authors: Rubio
authors: Department of Surgery, Miller School of Medicine, University of Miami, Miami, Fla.
authors: Sharon J
authors: SJ
authors: Elliot
mesh_terms: D000375:Aging / Q000473:pathology*; D000818:Animals; D017209:Apoptosis; D001835:Body Weight; D003367:Cotinine / Q000652:urine; D004579:Electron Transport; D004967:Estrogens / Q000172:deficiency*; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D006909:Hydroxyproline / Q000378:metabolism; D008168:Lung / Q000201:enzymology / Q000473:pathology*; D008264:Macrophages / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D008810:Mice, Inbred C57BL; D009929:Organ Size; D018384:Oxidative Stress; D011960:Receptors, Estrogen / Q000378:metabolism; D012907:Smoking / Q000009:adverse effects*; D014599:Uterus / Q000473:pathology
chemical_list: D004967:Estrogens; D011960:Receptors, Estrogen; D020778:Matrix Metalloproteinase 2; D003367:Cotinine; D006909:Hydroxyproline