The ontogeny of GAP-43 (neuromodulin) mRNA in postnatal rat brain: evidence for a sex dimorphism.

GAP-43 is a membrane-bound protein selectively concentrated in axonal growth cones during brain development and implicated in axonal outgrowth and elongation. A sex dimorphism in the number of synapses in certain regions of the adult rat brain has been attributed to differences in gonadal steroid hormone action during early postnatal life. The results of recent studies have demonstrated that gonadal steroids modulate GAP-43 mRNA in regions of the postnatal and adult brain where steroid hormone receptors are concentrated. Since gonadal steroids influence the development of the sexually undifferentiated brain during the first few weeks of postnatal life, the present study investigated the ontogeny of GAP-43 mRNA in the male and female rat brain between postnatal days 1 and 25. On postnatal days 1, 3, 6, 12, 18, and 25, brains were collected from male and female postnates and frozen, and 16 microns cryostat sections were processed and hybridized with a 35S-labeled antisense riboprobe complementary to GAP-43 mRNA. Evaluation of film autoradiograms demonstrated a widespread distribution of GAP-43 mRNA in postnatal brain regions, including the cerebral cortex; bed nucleus of the stria terminalis; and medial preoptic area, ventromedial nucleus, and arcuate nucleus of the hypothalamus. Densitometric measurements revealed that GAP-43 mRNA was transiently elevated during early postnatal life, with a subsequent decrease during brain maturation, although the pattern of change varied among the brain regions investigated. In addition, the level of GAP-43 hybridization signal was significantly higher in the male cortex, bed nucleus, and medial preoptic nucleus, but not the ventromedial and arcuate nuclei, than in postnatal females. Analysis of slide autoradiograms demonstrated that the change in GAP-43 mRNA during postnatal development was due to changes at the cellular level. The present results indicate that expression of GAP-43 mRNA is transiently elevated and sexually dimorphic in certain regions of the early postnatal rat brain. The results further suggest that the differential expression of GAP-43 in the male and female postnatal brain may be related to sex differences in neuronal outgrowth and connectivity resulting in a dimorphism in the pattern of adult neuronal circuitry.