PMID- 17881205 OWN - NLM STAT- MEDLINE DCOM- 20080201 LR - 20151119 IS - 0940-2993 (Print) IS - 0940-2993 (Linking) VI - 59 IP - 3-4 DP - 2007 Nov TI - Nicotine-induced prenatal overexposure to maternal glucocorticoid and intrauterine growth retardation in rat. PG - 245-51 AB - Overexposure to glucocorticoid during fetal development can result in intrauterine growth retardation (IUGR) as well as other diseases after birth. The purpose of this study is to investigate the possibility of glucocorticoid disturbance-mediated nicotine-induced IUGR after chronic prenatal exposure. Nicotine at 1.0mg/kg twice a day was administered subcutaneously to pregnant rats from gestational day (GD) 8 to GD 15 (mid-gestation) or GD 21 (late-gestation). Placental weights and fetal developmental parameters were recorded. Corticosterone levels were determined by radioimmunoassay. The mRNA expressions of adrenal steroidogenic acute regulatory protein (StAR), cytochrome P450 cholesterol side chain cleavage (P450scc) and placental 11 beta-hydroxysteroid dehydrogenase type 2 (11 beta-HSD-2) were determined using real-time quantitative RT-PCR. The results showed that prenatal chronic nicotine exposure causes IUGR in rats (P<0.01); in response to nicotine exposure, maternal serum corticosterone levels were elevated at mid- and late-gestations (P<0.05); mRNA expressions of StAR and P450scc increased in maternal adrenals (P<0.05 or 0.01) but decreased in fetal adrenals (P=0.16 or 0.11). Furthermore, the mRNA levels of placental 11 beta-HSD-2 were reduced at mid- and late-gestations (P<0.05). These results suggest that nicotine-induced IUGR is associated with the disturbances of glucocorticoid homeostasis in maternal and fetal rats. A possible underlying mechanism is that long term nicotine administration leads to fetal overexposure to maternal glucocorticoid by the combined effect of increased maternal glucocorticoid level and impaired placental barrier to it, all of which eventually leads to the fetal adrenocortical dysfunction and IUGR. FAU - Chen, Man AU - Chen M AD - Department of Pharmacology, Basic Medical School of Wuhan University, Donghu Road 115(#) Hubei Province Wuhan 430071, China. FAU - Wang, Ting AU - Wang T FAU - Liao, Zhang-Xiu AU - Liao ZX FAU - Pan, Xiao-Liang AU - Pan XL FAU - Feng, Ying-Hong AU - Feng YH FAU - Wang, Hui AU - Wang H LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20070919 PL - Germany TA - Exp Toxicol Pathol JT - Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie JID - 9208920 RN - 0 (Nicotinic Agonists) RN - 0 (Phosphoproteins) RN - 0 (steroidogenic acute regulatory protein) RN - 6M3C89ZY6R (Nicotine) RN - EC 1.1.1.146 (11-beta-Hydroxysteroid Dehydrogenase Type 2) RN - EC 1.14.15.6 (Cholesterol Side-Chain Cleavage Enzyme) RN - W980KJ009P (Corticosterone) SB - IM MH - 11-beta-Hydroxysteroid Dehydrogenase Type 2/genetics/metabolism MH - Adrenal Glands/drug effects/embryology/metabolism MH - Animals MH - Cholesterol Side-Chain Cleavage Enzyme/genetics/metabolism MH - Corticosterone/*blood MH - Disease Models, Animal MH - Female MH - Fetal Development/drug effects MH - Fetal Growth Retardation/*chemically induced/pathology MH - Fetal Weight/drug effects MH - Gene Expression Regulation, Developmental/drug effects MH - Injections, Subcutaneous MH - *Maternal Exposure MH - Maternal-Fetal Exchange/*drug effects/physiology MH - Nicotine/*toxicity MH - Nicotinic Agonists/*toxicity MH - Organ Size/drug effects MH - Phosphoproteins/genetics/metabolism MH - Placenta/drug effects/enzymology/pathology MH - Pregnancy MH - Rats MH - Rats, Wistar MH - Specific Pathogen-Free Organisms EDAT- 2007/09/21 09:00 MHDA- 2008/02/02 09:00 CRDT- 2007/09/21 09:00 PHST- 2007/03/12 00:00 [received] PHST- 2007/05/11 00:00 [accepted] PHST- 2007/09/21 09:00 [pubmed] PHST- 2008/02/02 09:00 [medline] PHST- 2007/09/21 09:00 [entrez] AID - S0940-2993(07)00039-5 [pii] AID - 10.1016/j.etp.2007.05.007 [doi] PST - ppublish SO - Exp Toxicol Pathol. 2007 Nov;59(3-4):245-51. doi: 10.1016/j.etp.2007.05.007. Epub 2007 Sep 19.