title: Nicotine-induced over-exposure to maternal glucocorticoid and activated glucocorticoid metabolism causes hypothalamic-pituitary-adrenal axis-associated neuroendocrine metabolic alterations in fetal rats.
abstract: Fetuses with intrauterine growth retardation (IUGR) induced by prenatal nicotine exposure are susceptible to adult metabolic syndrome. Our goals for this study were to investigate the effects of prenatal nicotine exposure on the fetal hypothalamic-pituitary-adrenal (HPA) axis and glucose and lipid metabolism and to explain the susceptibility to adult metabolic syndrome for fetuses with nicotine induced-IUGR. Pregnant Wistar rats were administered 0.25, 0.5, and 1.0 mg/kg nicotine subcutaneously twice a day from gestational day 11 to 20. Nicotine exposure significantly increased the levels of fetal blood corticosterone and decreased the expression of placental 11β-hydroxysteroid dehydrogenase-2 (11β-HSD-2). Moreover, nicotine exposure significantly increased the expressions of fetal hippocampal 11β-HSD-1 and glucocorticoid receptor (GR) and decreased the expressions of fetal hypothalamus corticotropin-releasing hormone, adrenal steroid acute regulatory protein, and cholesterol side-chain cleavage enzyme. Additionally, increased expressions of 11β-HSD-1 and GR were observed in fetal liver and gastrocnemius muscle, and these tissues also expressed lower levels of insulin-like growth factor-1 (IGF-1), IGF-1 receptor, and insulin receptor, while expressing increased levels of adiponectin receptor, leptin receptors, and AMP-activated protein kinase α2. Prenatal nicotine exposure causes HPA axis-associated neuroendocrine metabolic alterations in fetal rats. The underlying mechanism may involve activated glucocorticoid metabolism in various fetal tissues.
authors.affiliation: Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071, China.
authors.forename: D
authors.initials: D
authors.lastname: Xu
authors.forename: G
authors.initials: G
authors.lastname: Liang
authors.forename: Y E
authors.initials: YE
authors.lastname: Yan
authors.forename: W W
authors.initials: WW
authors.lastname: He
authors.forename: Y S
authors.initials: YS
authors.lastname: Liu
authors.forename: L B
authors.initials: LB
authors.lastname: Chen
authors.forename: J
authors.initials: J
authors.lastname: Magdalou
authors.forename: H
authors.initials: H
authors.lastname: Wang
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000235:genetics; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000235:genetics; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D004305:Dose-Response Relationship, Drug; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D047109:Fetal Development / Q000187:drug effects*; D005317:Fetal Growth Retardation / Q000097:blood / Q000139:chemically induced / Q000378:metabolism; D005865:Gestational Age; D005938:Glucocorticoids / Q000097:blood / Q000378:metabolism*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D007279:Injections, Subcutaneous; D018811:Maternal Exposure / Q000009:adverse effects*; D008431:Maternal-Fetal Exchange; D009489:Neurosecretion / Q000187:drug effects*; D009538:Nicotine / Q000633:toxicity*; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D010920:Placenta / Q000201:enzymology / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D001786:Blood Glucose; D005938:Glucocorticoids; D009538:Nicotine; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2