PMID- 32445661
OWN - NLM
STAT- MEDLINE
DCOM- 20200723
LR  - 20200723
IS  - 1879-3169 (Electronic)
IS  - 0378-4274 (Linking)
VI  - 331
DP  - 2020 Oct 1
TI  - Programming of a developmental imbalance in hypothalamic glutamatergic/GABAergic 
      afferents mediates low basal activity of the hypothalamic-pituitary-adrenal axis 
      induced by prenatal dexamethasone exposure in male offspring rats.
PG  - 33-41
LID - S0378-4274(20)30171-5 [pii]
LID - 10.1016/j.toxlet.2020.05.022 [doi]
AB  - This study was intended to demonstrate that prenatal dexamethasone exposure (PDE) 
      can induce low basal activity of the hypothalamic-pituitary-adrenal axis (HPAA) 
      in male offspring rats and explore the underlying mechanism. Pregnant rats were 
      subcutaneously administered 0.2 mg/kg/d dexamethasone from gestational day (GD) 9 
      to GD20. Male GD20 fetuses and postnatal day 85 adult male offspring rats were 
      sacrificed under anesthesia. Hypothalamic cells were from GD20 approximately postnatal day (PD) 
      7 fetal male rats, treated with different concentrations of dexamethasone and the 
      glucocorticoid receptor (GR) antagonist mifepristone for 5 days. The results 
      suggested that dexamethasone enhanced the expression of hypothalamic L-glutamic 
      acid decarboxylase (GAD) 67 by activating GR, further stimulating the conversion 
      of glutamate to gamma-aminobutyric acid (GABA) and inducing an imbalance in 
      glutamatergic/GABAergic afferents in the hypothalamic paraventricular nucleus 
      (PVN). This imbalance change was maintained postnatally, leading to the 
      inhibition of parvocellular neurons, and mediating the low basal activity of the 
      HPAA in PDE offspring rats, which was manifested by decreased levels of blood 
      adrenocorticotropic hormone and corticosterone as well as reduced expression 
      levels of corticotrophin-releasing hormone (CRH) and arginine vasopressin (AVP) 
      in the hypothalamus. Programming of a developmental imbalance in 
      glutamatergic/GABAergic afferents in the PVN is a potential mechanism responsible 
      for low basal activity of the HPAA in male PDE rats.
CI  - Copyright (c) 2020. Published by Elsevier B.V.
FAU - Lu, Juan
AU  - Lu J
AD  - Jiangmen Central Hospital Affiliated Jiangmen Hospital of Sun YAT-SEN University, 
      Jiangmen, 529000, China; Department of Pharmacology, Wuhan University School of 
      Basic Medical Sciences, Wuhan, 430071, China; Gansu provincial hospital of TCM 
      Affiliated to Gansu University of Chinese Medicine, Gansu, 730050, China.
FAU - Li, Qiang
AU  - Li Q
AD  - Gansu provincial hospital of TCM Affiliated to Gansu University of Chinese 
      Medicine, Gansu, 730050, China.
FAU - Xu, Dan
AU  - Xu D
AD  - Department of Pharmacology, Wuhan University School of Basic Medical Sciences, 
      Wuhan, 430071, China; Hubei Provincial Key Laboratory of Developmentally 
      Originated Disease, Wuhan, 430071, China.
FAU - Liao, Yongbin
AU  - Liao Y
AD  - Jiangmen Central Hospital Affiliated Jiangmen Hospital of Sun YAT-SEN University, 
      Jiangmen, 529000, China. Electronic address: lybjm59@aliyun.com.
FAU - Wang, Hui
AU  - Wang H
AD  - Department of Pharmacology, Wuhan University School of Basic Medical Sciences, 
      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
DEP - 20200521
PL  - Netherlands
TA  - Toxicol Lett
JT  - Toxicology letters
JID - 7709027
RN  - 113-79-1 (Arginine Vasopressin)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - 56-12-2 (gamma-Aminobutyric Acid)
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - 9002-60-2 (Adrenocorticotropic Hormone)
RN  - EC 4.1.1.15 (Glutamate Decarboxylase)
RN  - EC 4.1.1.15 (glutamate decarboxylase 1)
RN  - W980KJ009P (Corticosterone)
SB  - IM
MH  - Adrenocorticotropic Hormone/blood
MH  - Animals
MH  - Animals, Newborn
MH  - Arginine Vasopressin/metabolism
MH  - Corticosterone/blood
MH  - Dexamethasone/*toxicity
MH  - Female
MH  - Fetal Development/drug effects
MH  - Fetal Growth Retardation/chemically induced/metabolism
MH  - Glutamate Decarboxylase/metabolism
MH  - Glutamic Acid/*metabolism
MH  - Hypothalamo-Hypophyseal System/*drug effects/embryology/metabolism
MH  - Male
MH  - Neurons, Afferent/*drug effects/metabolism
MH  - Paraventricular Hypothalamic Nucleus/*drug effects/embryology/metabolism
MH  - Pituitary-Adrenal System/*drug effects/embryology/metabolism
MH  - Pregnancy
MH  - Prenatal Exposure Delayed Effects/chemically induced/*metabolism
MH  - Rats
MH  - gamma-Aminobutyric Acid/*metabolism
OTO - NOTNLM
OT  - Dexamethasone
OT  - Glutamatergic/GABAergic afferents
OT  - Hypothalamic-pituitary-adrenal axis
OT  - Hypothalamus
OT  - Low basal activity
OT  - Programming
EDAT- 2020/05/24 06:00
MHDA- 2020/07/24 06:00
CRDT- 2020/05/24 06:00
PHST- 2020/01/21 00:00 [received]
PHST- 2020/05/14 00:00 [revised]
PHST- 2020/05/18 00:00 [accepted]
PHST- 2020/05/24 06:00 [pubmed]
PHST- 2020/07/24 06:00 [medline]
PHST- 2020/05/24 06:00 [entrez]
AID - S0378-4274(20)30171-5 [pii]
AID - 10.1016/j.toxlet.2020.05.022 [doi]
PST - ppublish
SO  - Toxicol Lett. 2020 Oct 1;331:33-41. doi: 10.1016/j.toxlet.2020.05.022. Epub 2020 
      May 21.