Glucocorticoids are insufficient for neonatal gene induction in the liver.
Glucocorticoids and their receptor (GR) play a key role in perinatal gene induction. In the liver, the GR is essential for the neonatal induction of a number of genes, including that coding for tyrosine aminotransferase (TAT). To assess the function of the GR in the perinatal period, we have compared the activity of two types of glucocorticoid responsive elements in transgenic mice; one is the Tat gene glucocorticoid-responsive unit (GRU), an assembly of numerous binding sites for transcription factors, including the GR; the other is a simple dimer of high-affinity GR binding sites (GREs). Both elements confer strong glucocorticoid response in the adult liver. However, only the Tat GRUs are able to promote neonatal induction; the GRE dimer is unresponsive. Because this dimer is responsive to glucocorticoid administration in the neonate, the absence of neonatal induction is not due to the inactivity of the GR at this stage. At birth, the neonate has to withstand a brief period of starvation and hypoglycemia, a nutritional and hormonal situation that resembles fasting in the adult. In transgenic mice, the responses at birth and after fasting in the adult are similar: the Tat GRUs but not the dimeric GREs are activated. Our results show that, in rodents, glucocorticoids are not sufficient for neonatal gene induction in the liver and support the conclusion that the hypoglycemia at birth is the main trigger for expression.
Sassi
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Institut Jacques Monod du Centre National de la Recherche Scientifique, Université Paris 7, Tour 43, 2 Place Jussieu, 75251 Paris Cedex 05, France.
Pictet
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R
Grange
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D000818:Animals; D000831:Animals, Newborn; D004247:DNA / Q000378:metabolism; D019281:Dimerization; D005508:Food Deprivation; D018507:Gene Expression Regulation, Developmental; D005938:Glucocorticoids / Q000502:physiology*; D007003:Hypoglycemia / Q000235:genetics; D008099:Liver / Q000254:growth & development*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D016385:TATA Box; D015533:Transcriptional Activation
D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D004247:DNA