Gonadal steroids modulate the growth-associated protein GAP-43 (neuromodulin) mRNA in postnatal rat brain

Gonadal steroid hormone action during early postnatal life determines the growth and connectivity of certain neuronal populations in the hypothalamus. The results of recent studies indicate that steroid hormones modulate the growth-associated protein GAP-43 mRNA in the adult rodent hypothalamus. Since GAP-43 is concentrated in axonal growth cones and has been implicated in axonal elongation and synaptogenesis, the present study investigated the effect of various gonadal hormonal conditions on GAP-43 mRNA levels in postnatal rat brain. On postnatal day 1, male rats were castrated or sham-operated and injected with sesame oil. Additional intact female rats were also injected with oil, while a group of female pups were injected with testosterone propionate. On postnatal day 6, brains were frozen and 16-μm cryostat sections processed and hybridized with a ³⁵S-labeled antisense riboprobe complimentary to GAP-43 mRNA. Slide-mounted sections were stringently washed, apposed to X-ray film and then dipped in liquid emulsion. Evaluation of slide and film autoradiograms revealed an extensive presence of GAP-43 mRNA in the medial preoptic nucleus, bed nucleus of the stria terminalis and cerebral cortex, while the intensity of hybridization signal in other brain regions including the striatum was low. Quantitative assessment of GAP-43 mRNA in the medial preoptic area revealed that the level of GAP-43 mRNA was highest in the sham-operated male, attenuated after male castration, low in the intact female and markedly augmented in the testosterone-treated female. The pattern of change in the bed nucleus of the stria terminalis and laminae II and III of the frontal cortex was similar to that observed in the preoptic area. The changes in hybridization signal were positively correlated with changes in serum testosterone levels as determined by RIA. The results of these studies indicate that GAP-43 mRNA levels in the medial preoptic area, bed nucleus of the stria terminalis and cerebral cortex are sexually dimorphic and modulated by changes in gonadal steroid hormone levels. The results further suggest that the differential regulation of GAP-43 mRNA by sex steroids in the male and female postnatal brain may influence the phenotype of forebrain neuronal circuitry and thereby determine the phenotype of adult neuronal function.