Effect of progesterone, testosterone and their 5α-reduced metabolites on GFAP gene expression in type 1 astrocytes

Abstract

Astrocytes possess steroid receptors as well as several enzymes typical of steroid target cells, such as 5α-reductase, which converts testosterone (T) and progesterone (P) into their respective 5α-reduced metabolites, and the 3α-hydroxysteroid dehydrogenase (3α-HSD). Because of this, it was deemed of interest to analyze whether the original hormones P and T, and their 5α-reduced metabolites dihydrotestosterone (DHT), 5α-androstan-3α,17β-diol (3α-diol), dihydroprogesterone (DHP) and 5α-pregnan-3α-ol-20-one (THP), might exert some effects on the expression of the most typical astrocytec marker, i.e. the glial fibrillary acidic protein WAY). Cultures of rat type 1 astrocytes were exposed to the various steroids for 2, 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 appeared more promptly (at 2 h) than that of P (at 6 h). This result suggests that the effect of P might be linked to its conversion into DHP; this hypothesis has been confirmed by showing that the addition of finasteride (a specific blocker of the 5α-reductase) is able to completely abolish the effect of P. After exposure to DHP or THP, a decrease of GFAP gene expression was observed at later intervals (24 h). In the case of androgens, T and 3α-diol did not change GFAP expression at any time of exposure, while DHT produced a significant decrease of GFAP mRNA only after 24 h of exposure. Taken together, the data indicate that the 5α-reduced metabolites of P and T may modulate the expression of GFAP in type 1 rat astrocytes.