Androgens selectively modulate C-fos messenger RNA induction in the rat hippocampus following novelty.

We have previously shown that androgen receptors are found in high concentrations in hippocampal CA1 pyramidal cells. To begin to explore the possible roles for androgen receptors in this area of the brain, we studied the effects of endogenous and exogenous androgen on the behaviourally induced expression of cellular immediate early gene messenger RNAs. Adult male Fischer 344 rats were either gonadectomized, gonadectomized and given two Silastic capsules of dihydrotestosterone propionate at the time of surgery, or left intact. Three weeks later, animals were placed into a novel open field for 20 min. This behavioural paradigm caused region- and gene-specific increases of c-fos, jun-B, c-jun and zif268 messenger RNA in the hippocampus as determined by semi-quantitative in situ hybridization histochemistry. The removal of circulating androgen by gonadectomy potentiated, whereas dihydrotestosterone treatment of castrates attenuated, the behaviourally induced expression of c-fos messenger RNA in the CA1 region of the hippocampus. No changes in c-fos messenger RNA expression were detected in the CA3 or dentate gyrus regions where androgen receptor levels are low. Androgen status did not affect either the basal or stimulated expression of Jun-B, c-Jun or zif268 messenger RNA in any of the three cellular regions of the hippocampus examined. These results implicate androgen receptors in modulating the active response of hippocampal neurons to a behaviourally relevant stimulus. Since the products of cellular immediate genes can function to alter an array of downstream genes, the modulation of these genes in the hippocampus by gonadal hormones may have important ramifications for hippocampal function.