GLUCOCORTICOID ADMINISTRATION ALTERS NUCLEAR TRANSCRIPTION FACTORS INFETAL-RAT BRAIN - IMPLICATIONS FOR THE USE OF ANTENATAL STEROIDS

A recent Consensus Conference endorsed antenatal steroid use in premat urity, but indicated the need for future work on molecular and cellula r effects on the developing brain. in the current study, pregnant rats were given dexamethasone during late gestation, in doses spanning tho se recommended for use, and effects on nuclear transcription factors w ere evaluated. Within the first hour after a single dose of dexamethas one, and intensifying over 4 h, marked induction of brain c-Sos was se en. With repeated administration, c-fos became suppressed in some brai n regions, but remained elevated in others. Dexamethasone also elicite d suppression of the AP-1 family of nuclear binding proteins, but with a slower time course than seen for c-Sos induction. The magnitude of the effects of late gestational exposure to dexamethasone on these tra nscription factors was comparable to those seen when repeated doses we re administered to midgestation embryos in the context of dysmorphogen esis. Similarly, the effects on brain c-fos expression were substantia lly greater than those in the liver, an archetypal glucocorticoid targ et tissue. These results indicate that even a single, low dose of gluc ocorticoids used in late gestation, can disrupt the transcription fact ors that regulate brain cell differentiation. (C) 1998 Elsevier Scienc e B.V. All rights reserved.