PMID- 31075344
OWN - NLM
STAT- MEDLINE
DCOM- 20200515
LR  - 20200515
IS  - 1096-0333 (Electronic)
IS  - 0041-008X (Linking)
VI  - 375
DP  - 2019 Jul 15
TI  - Glucocorticoid programming mechanism for hypercholesterolemia in prenatal 
      ethanol-exposed adult offspring rats.
PG  - 46-56
LID - S0041-008X(19)30165-6 [pii]
LID - 10.1016/j.taap.2019.05.002 [doi]
AB  - Our previous studies showed that prenatal ethanol exposure (PEE) elevated blood 
      total cholesterol (TCH) level in adult offspring rats. This study was aimed at 
      elucidating the intrauterine programming mechanism of hypercholesterolemia in 
      adult rats induced by PEE. Pregnant Wistar rats were intragastrically 
      administered ethanol (4 mg/kg∙d) from gestational day (GD) 9 to 20. The offspring 
      rats were euthanized at GD20 and postnatal week 24. Results showed that PEE 
      decreased serum TCH and HDL-C levels (female and male) as well as LDL-C level 
      (female only) in fetal rats but increased serum TCH level and the TCH/HDL-C and 
      LDL-C/HDL-C ratios in adult rats. Furthermore, PEE elevated serum corticosterone 
      levels but inhibited hepatic insulin-like growth factor 1 (IGF1) signaling 
      pathway, cholesterol synthesis and output in fetal rats. The conversed changes 
      were observed in adult rats. Moreover, histone acetylation (H3K9ac and H3K14ac) 
      and expression of hepatic reverse cholesterol transport (RCT) related genes, 
      scavenger receptor BI and low-density lipoprotein receptor were decreased before 
      and after birth by PEE. In HepG2 cells, cortisol negatively regulated the IGF1 
      signaling pathway and cholesterol metabolic genes, but this inhibition of the 
      cholesterol metabolic genes could be reversed by glucocorticoid receptor 
      antagonist RU486, whereas exogenous IGF1 treatment only reversed the 
      downregulation of RCT genes by cortisol. We confirmed a "two programming" 
      mechanism for PEE-induced hypercholesterolemia in adult rats. The "first 
      programming" was a glucocorticoid (GC)-induced persistent reduction of RCT genes 
      by epigenetic modifications, and the "second programming" was the negative 
      regulation of cholesterol synthesis and output by the GC-IGF1 axis.
CI  - Copyright (c) 2019 Elsevier Inc. All rights reserved.
FAU - Hu, Shuwei
AU  - Hu S
AD  - Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 
      430071, China.
FAU - Qin, Jun
AU  - Qin J
AD  - Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 
      430071, China; Hubei Provincial Key Laboratory of Developmentally Originated 
      Disease, Wuhan 430071, China.
FAU - Zhou, Jin
AU  - Zhou J
AD  - Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 
      430071, China.
FAU - Magdalou, Jacques
AU  - Magdalou J
AD  - UMR 7561, CNRS-Universite de Lorraine, Faculte de Medicine, Vandoeuvre-les-Nancy, 
      France.
FAU - Chen, Liaobin
AU  - Chen L
AD  - Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 
      430071, China; Hubei Provincial Key Laboratory of Developmentally Originated 
      Disease, Wuhan 430071, China.
FAU - Xu, Dan
AU  - Xu D
AD  - Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 
      430071, China; Hubei Provincial Key Laboratory of Developmentally Originated 
      Disease, Wuhan 430071, China. Electronic address: xuyidan70188@whu.edu.cn.
FAU - Wang, Hui
AU  - Wang H
AD  - Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 
      430071, China; Hubei Provincial Key Laboratory of Developmentally Originated 
      Disease, Wuhan 430071, China. Electronic address: wanghui19@whu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190508
PL  - United States
TA  - Toxicol Appl Pharmacol
JT  - Toxicology and applied pharmacology
JID - 0416575
RN  - 0 (Glucocorticoids)
RN  - 0 (Histones)
RN  - 0 (Somatomedins)
RN  - 3K9958V90M (Ethanol)
RN  - 97C5T2UQ7J (Cholesterol)
SB  - IM
MH  - Acetylation
MH  - Animals
MH  - Cholesterol/*blood
MH  - Ethanol/*toxicity
MH  - Female
MH  - Fetal Blood
MH  - Gene Expression Regulation, Developmental/drug effects
MH  - Glucocorticoids/*metabolism
MH  - Hep G2 Cells
MH  - Histones/metabolism
MH  - Humans
MH  - Hypercholesterolemia/*etiology
MH  - Liver/drug effects/metabolism
MH  - Male
MH  - Pregnancy
MH  - *Prenatal Exposure Delayed Effects
MH  - Rats
MH  - Rats, Wistar
MH  - Somatomedins
MH  - Specific Pathogen-Free Organisms
OTO - NOTNLM
OT  - Glucocorticoid
OT  - Hepatic cholesterol metabolism
OT  - Histone acetylation
OT  - Hypercholesterolemia
OT  - Insulin-like growth factor 1
EDAT- 2019/05/11 06:00
MHDA- 2020/05/16 06:00
CRDT- 2019/05/11 06:00
PHST- 2019/01/25 00:00 [received]
PHST- 2019/04/18 00:00 [revised]
PHST- 2019/05/06 00:00 [accepted]
PHST- 2019/05/11 06:00 [pubmed]
PHST- 2020/05/16 06:00 [medline]
PHST- 2019/05/11 06:00 [entrez]
AID - S0041-008X(19)30165-6 [pii]
AID - 10.1016/j.taap.2019.05.002 [doi]
PST - ppublish
SO  - Toxicol Appl Pharmacol. 2019 Jul 15;375:46-56. doi: 10.1016/j.taap.2019.05.002. 
      Epub 2019 May 8.