beta Adrenergic control of c-fos protooncogene expression in developing rat brain regions.

The protooncogene c-fos encodes a nuclear protein that acts as a powerful enhancer of gene transcription, and shares the same general patterns of reactivity to stimulation as ornithine decarboxylase, an essential enzyme in cell replication and differentiation; c-fos enhances expression of proteins whose genes possess the AP-1 consensus sequence, which include ornithine decarboxylase. In the current study, we examined the regulation of c-fos during early postnatal development of the rat central nervous system. Regional profiles of basal c-fos mRNA paralleled the ontogenetic profiles of cell replication and differentiation; in the earliest developing region (midbrain + brainstem) c-fos was low by birth and did not change over the first 2 postnatal weeks; in the forebrain, where replication and differentiation peak somewhat later, c-fos levels were higher during the first postnatal week than in the second; in the latest developing region (cerebellum), basal c-fos expression was low at birth and increased markedly during the second postnatal week, coincidentally with the increase in neuronal cell replication/differentiation. The resemblance of these patterns to those of ornithine decarboxylase, which is regulated in part by beta adrenergic input, led us to evaluate the potential role of beta receptors in the ontogenetic control of c-fos. In the forebrain of 2-day-old rats, intracisternal administration of isoproterenol, a beta adrenergic agonist, produced > 20-fold stimulation of c-fos within 10 min of drug administration. The induction was mediated through the beta receptor, as confirmed by studies with selective adrenergic blocking agents, and could be reproduced by administration of cAMP analogs.(ABSTRACT TRUNCATED AT 250 WORDS)

Duke Scholars

Author Frederic J. Seidler Pharmacology & Cancer Biology

Author Frederick Schachat Cell Biology

Author Theodore Alan Slotkin Pharmacology & Cancer Biology