GLUCOCORTICOIDS ARE INSUFFICIENT FOR NEONATAL GENE INDUCTION IN THE LIVER

Glucocorticoids and their receptor (GR) play a key role in perinatal g ene induction. In the liver, the GR is essential for the neonatal indu ction of a number of genes, including that coding for tyrosine aminotr ansferase (TAT), To assess the function of the GR in the perinatal per iod, we have compared the activity of two types of glucocorticoid resp onsive elements in transgenic mice; one is the Tat gene glucocorticoid responsive unit (GRU), an assembly of numerous binding sites for tran scription factors, including the GR; the other is a simple dimer of hi gh-affinity GR binding sites (GREs), Both elements confer strong gluco corticoid response in the adult liver. However, only the Tat GRUs are able to promote neonatal induction; the GRE dimer is unresponsive. Bec ause this dimer is responsive to glucocorticoid administration in the neonate, the absence of neonatal induction is not due to the inactivit y of the GR at this stage. At birth, the neonate has to withstand a br ief 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 Ta t GRUs but not the dimeric GREs are activated. Our results show that, in rodents, glucocorticoids are not sufficient for neonatal gene induc tion in the liver and support the conclusion that the hypoglycemia at birth is the main trigger for expression.