GLUCOCORTICOID REGULATION OF ANGIOTENSINOGEN GENE-EXPRESSION IN DISCRETE AREAS OF THE MALE-RAT BRAIN - AN IN-SITU HYBRIDIZATION STUDY

The regulation of angiotensinogen gene expression by glucocorticoids has been described in several studies. Kalinyak and Perlman reported on a 60% increase of angiotensinogen expression in the rat brain after dexamethasone treatment with a single, high-dose injection. The purpose of the present study was to investigate whether a general upregulation of angiotensinogen expression or a region-specific upregulation underlies these findings. By using in situ hybridization and computer-assisted microdensitometry we evaluated the regional changes in angiotensinogen expression following dexamethasone treatment. Angiotensinogen expression was strongly stimulated in several areas (medial septum and locus ceruleus), while only moderately in others (hypothalamus, medulla). An interesting finding is the difference in glucocorticoid receptor regulation among the circumventricular organs. The subfornical organ displayed no changes in angiotensinogen-mRNA, whereas the area postrema showed an increase. Furthermore, the angiotensinogen expression in the median eminence decreased substantially. The nature of these effects will form the subject of further investigations. In conclusion we demonstrated an overall increase but certain heterogeneities in angiotensinogen expression after dexamethasone treatment, a pattern which suggests different degrees of glucocorticoid receptor regulation of the angiotensinogen gene in certain areas of the brain, probably mainly dependent on the degree of glial glucocorticoid receptor presence.