title: Metyrapone blocks maternal food restriction-induced changes in female rat offspring lung development.
abstract: Maternal food restriction (MFR) during pregnancy affects pulmonary surfactant production in the intrauterine growth-restricted (IUGR) offspring through unknown mechanisms. Since pulmonary surfactant production is regulated by maternal and fetal corticosteroid levels, both known to be increased in IUGR pregnancies, we hypothesized that metyrapone (MTP), a glucocorticoid synthesis inhibitor, would block the effects of MFR on surfactant production in the offspring. Three groups of pregnant rat dams were used (1) control dams fed ad libitum; (2) MFR (50% reduction in calories) from days 10 to 22 of gestation; and (3) MFR + MTP in drinking water (0.5 mg/mL), days 11 to 22 of gestation. At 5 months, the MFR offspring weighed significantly more, had reduced alveolar number, increased septal thickness, and decreased surfactant protein and phospholipid synthesis. These MFR-induced effects were normalized by the antiglucocorticoid MTP, suggesting that the stress of MFR causes hypercorticoidism, altering lung structure and function in adulthood.
authors.affiliation: 1Departments of Pediatrics and Obstetrics and Gynecology, LABioMed at Harbor-UCLA Medical Center, Torrance, CA, USA.
authors.forename: Virender K
authors.initials: VK
authors.lastname: Rehan
authors.forename: Yishi
authors.initials: Y
authors.lastname: Li
authors.forename: Julia
authors.initials: J
authors.lastname: Corral
authors.forename: Aditi
authors.initials: A
authors.lastname: Saraswat
authors.forename: Sumair
authors.initials: S
authors.lastname: Husain
authors.forename: Ankita
authors.initials: A
authors.lastname: Dhar
authors.forename: Reiko
authors.initials: R
authors.lastname: Sakurai
authors.forename: Omid
authors.initials: O
authors.lastname: Khorram
authors.forename: John S
authors.initials: JS
authors.lastname: Torday
mesh_terms: D000367:Age Factors; D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D031204:Caloric Restriction; D005260:Female; D005865:Gestational Age; D008168:Lung / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D039382:Maternal Nutritional Physiological Phenomena; D008797:Metyrapone / Q000494:pharmacology*; D010743:Phospholipids / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D037661:Pulmonary Surfactant-Associated Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012737:Sex Factors; D065088:Steroid Synthesis Inhibitors / Q000494:pharmacology*; D046509:Tissue Culture Techniques; D015430:Weight Gain
chemical_list: D010743:Phospholipids; D037661:Pulmonary Surfactant-Associated Proteins; D065088:Steroid Synthesis Inhibitors; D008797:Metyrapone
keywords: corticosterone; intrauterine growth restriction; lung development; maternal food restriction; metyrapone
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