Regulation of glucocorticoid-related genes and receptors/regulatory enzyme expression in intrauterin

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  Background: This study aims to explore factors that influence glucocorticoid (GC)-related genes and receptors/regulatory enzyme expression in intrauterine growth restriction (IUGR) filial rats.Method: An IUGR animal model was established by starvation, and brain tissue was removed after birth.Affymetrix Rat Gene 2.0 ST microarray was used to screen different expressions of GC-related genesin IUGR brain tissues.The mRNA and protein levels of related genes were validated by RT-PCR and western blot.Results: Results of the microarray revealed that the expression of 11β-Hsd2 was significantly downregulated in the IUGR groupcompared to the control group.Although Nr3clexhibited an overexpression trend in the IUGR group, there were no significant differences between the two groups.Further analysis suggests that the 11β-Hsd2 was negatively correlated to Nr3c1.In the transcription level, the expression level of 11β-Hsd2 mRNA decreased in the IUGR group,while the mRNA expression level of Nr3cl significantly increased.In the protein level, the expression of 11β-Hsd2 significantly decreased in the IUGR group;while the expression of Nr3cl significantly increased in the IUGR group.However, there were no significant differences in Nr3clphosphorylated at S211 and S266 between the IUGR andcontrol groups.Conclusion: The expression of Nr3cl was mainly regulatedby 11β-Hsd2, which could significantly inhibit its expression in IUGR rats.Phosphorylation on site S211 was the major activated form of Nr3cl.We speculatethat IUGR brain damage was caused by excessive amounts of GC due to significantactivation by Nr3cl.
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