EFFECT OF PROGESTERONE, TESTOSTERONE AND THEIR 5-ALPHA-REDUCED METABOLITES ON GFAP GENE-EXPRESSION IN TYPE-1 ASTROCYTES

Astrocytes possess steroid receptors as well as several enzymes typica l of steroid target cells, such as 5 alpha-reductase, which converts t estosterone (T) and progesterone (P) into their respective 5 alpha-red uced metabolites, and the 3 alpha-hydroxysteroid dehydrogenase (3 alph a-HSD). Because of this, it was deemed of interest to analyze whether the original hormones P and T, and their 5 alpha-reduced metabolites d ihydrotestosterone (DHT), 5 alpha-androstan-3 alpha,17 beta-diol (3 al pha-diol), dihydroprogesterone (DHP) and 5 alpha-pregnan-3 alpha-ol-2O -one (THP), might exert some effects on the expression of the most typ ical astrocytic market, i.e. the glial fibrillary acidic protein (GFAP ). Cultures of rat type I astrocytes were exposed to the various stero ids for 3, 6, and 24 h, and the variations of GFAP mRNA were measured by Northern blot analysis. A significant elevation of GFAP mRNA levels was observed after exposure to either P or DHP; the effect of DHP app eared more promptly (at 2 h) than that of P (at 6 h). This result sugg ests that the effect of P might be linked to its conversion into DHP; this hypothesis has been confirmed by showing that the addition of fin asteride (a specific blocker of the 5 alpha-reductase) is able to comp letely abolish the effect of P. After exposure to DHP or THP, a decrea se of GFAP gene expression was observed at later intervals (24 h). In the case of androgens, T and 3 alpha-diol did not change GFAP expressi on at any time of exposure, while DHT produced a significant decrease of GFAP mRNA only after 24 h of exposure. Taken together, the data ind icate that the 5 alpha-reduced metabolites of P and T may modulate the expression of GFAP in type 1 rat astrocytes.