Estrogen modulates the growth-associated protein GAP-43 (Neuromodulin) mRNA in the rat preoptic area and basal hypothalamus

Growth-associated protein GAP-43 is a membrane-bound phosphoprotein which has been implicated in axonal elongation and synaptogenesis. GAP-43 has been detected in the developing and adult preoptic area and basal hypothalamus. Since estrogen is thought to influence neuronal connectivity and synaptic remodeling in the hypothalamus, the present study investigated estrogen modulation of GAP-43 mRNA in the preoptic area and ventromedial nucleus of the adult hypothalamus. Female rats were bilateraly ovariecto-mized for 14 days and then treated for 96 h with sesame oil or 10 jig/100 g body weight of estradiol valerate. Treated animals as well as intact female and male rats were sacrificed, brains removed and coronal cryostat sections collected. Section-mounted slides were processed and hybridized with an antisense ³⁵S-labeled riboprobe complementary to GAP-43 mRNA. Additional slides were hybridized with an antisense ³⁵S-labeled riboprobe complementary to estrogen receptor mRNA. The slides were stringently washed, apposed to X-ray film and then dipped in liquid nuclear emulsion. Evaluation of film and slide autoradiograms revealed that GAP-43 and estrogen receptor mRNA are localized in similar regions of the medial preoptic area, arcuate nucleus and ventromedial nucleus of the hypothalamus. Quantitative assessment of GAP-43 mRNA in the medial preoptic area revealed that levels were elevated in the intact female, attenuated after ovariectomy and elevated in estrogen-treated ovariectomized animals. GAP-43 mRNA hybridization signal in the ventromedial nucleus of intact diestrus females and ovariectomized animals did not differ, but was augmented by estrogen treatment of ovariectomized females. In addition, GAP-43 mRNA in the male ventromedial nucleus, but not preoptic area, was significantly higher than levels in the intact female. The results of these studies indicate that estrogen modulates GAP-43 mRNA expression in the preoptic area and basal hypothalamus. Furthermore, these results suggest that changes in estrogen levels may alter GAP-43 biosynthesis, perhaps reflecting estrogen’s effect on the hypothalamic synaptic organization.