PMID- 10764636
OWN - NLM
STAT- MEDLINE
DCOM- 20000522
LR  - 20131121
IS  - 0041-008X (Print)
IS  - 0041-008X (Linking)
VI  - 164
IP  - 2
DP  - 2000 Apr 15
TI  - Glucocorticoid receptor regulation in the rat embryo: a potential site for 
      developmental toxicity?
PG  - 221-9
AB  - Glucocorticoids play a key role in controlling numerous cellular processes during 
      embryogenesis and fetal development. Excess glucocorticoids during development 
      have been linked to dysmorphogenesis and/or intrauterine growth impairment in 
      rodents. The actions of glucocorticoids are mediated by interaction with their 
      receptors. Negative feedback regulation of glucocorticoid receptor (GR) is 
      important for limiting cellular sensitivity to the hormones. Hence, acute 
      exposure of the adult rat to the synthetic glucocorticoid dexamethasone (DEX) 
      reduced both GR mRNA and protein in a variety of tissues that include hippocampus 
      and liver, in a dose- and time-dependent fashion. Reduction in GR mRNA and 
      protein were observable when DEX was given repeatedly at doses as low as 0. 05 
      mg/kg. In the control whole rat embryo, GR mRNA was low but measurable at as 
      early as gestational day (GD) 10, but underwent rapid ontogenetic increase in the 
      ensuring days. In contrast to the adult, neither GR mRNA nor protein in the whole 
      rat embryo was affected by acute or repeated DEX administration to pregnant rats 
      on GD10-13, even at doses as high as 0.8 mg/kg. Similar results were obtained in 
      embryonic palate and liver, tissues known to be glucocorticoid targets. These 
      data suggest that GR autoregulation does not occur during organogenesis in the 
      rat. Accordingly, hormonal elevations from stress or chemical insults can be 
      transduced unrestrictedly, ultimately leading to aberrant cell function and 
      development. The unique mode of GR regulation seen in the embryonic cells may 
      provide a potential common mechanism for developmental perturbation and toxicity 
      for a variety of insults.
FAU - Ghosh, B
AU  - Ghosh B
AD  - National Research Council, U.S. Environmental Protection Agency, Research 
      Triangle Park, North Carolina 27711, USA.
FAU - Wood, C R
AU  - Wood CR
FAU - Held, G A
AU  - Held GA
FAU - Abbott, B D
AU  - Abbott BD
FAU - Lau, C
AU  - Lau C
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Toxicol Appl Pharmacol
JT  - Toxicology and applied pharmacology
JID - 0416575
RN  - 0 (Glucocorticoids)
RN  - 0 (Receptors, Glucocorticoid)
RN  - 63231-63-0 (RNA)
RN  - 7S5I7G3JQL (Dexamethasone)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Dexamethasone/*toxicity
MH  - Down-Regulation/drug effects
MH  - Embryo, Mammalian/*drug effects
MH  - Female
MH  - Glucocorticoids/*toxicity
MH  - Hippocampus/drug effects/metabolism
MH  - Pregnancy
MH  - RNA/isolation & purification
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Glucocorticoid/*drug effects
MH  - Reverse Transcriptase Polymerase Chain Reaction
EDAT- 2000/04/15 09:00
MHDA- 2000/06/08 09:00
CRDT- 2000/04/15 09:00
PHST- 2000/04/15 09:00 [pubmed]
PHST- 2000/06/08 09:00 [medline]
PHST- 2000/04/15 09:00 [entrez]
AID - S0041-008X(00)98904-X [pii]
AID - 10.1006/taap.2000.8904 [doi]
PST - ppublish
SO  - Toxicol Appl Pharmacol. 2000 Apr 15;164(2):221-9. doi: 10.1006/taap.2000.8904.