Allopregnanolone promotes proliferation and differential gene expression in human glioblastoma cells.

Allopregnanolone (3α-THP) is one of the main reduced progesterone (P4) metabolites that is recognized as a neuroprotective and myelinating agent. 3α-THP also induces proliferation of different neural cells. It has been shown that P4 favors the progression of glioblastomas (GBM), the most common and aggressive primary brain tumors. However, the role of 3α-THP in the growth of GBMs is unknown. Here, we studied the effects of 3α-THP on the number of cells, proliferation and gene expression in U87 cell line derived from a human GBM. 3α-THP (10, 100nM and 1μM) increased the number of U87 cells, and at 10nM exerted a similar increase in both the number of total and proliferative U87 cells as compared with P4 (10nM). Interestingly, finasteride (F; 100nM), an inhibitor of 5α-reductase (5αR), an enzyme necessary to metabolize P4 and produce 3α-THP, blocked the increase in the number of U87 cells induced by P4. By using RT-qPCR, we determined that U87 cells express 5α-R isoenzymes 1 and 2 (5αR1 and 5αR2), being 5αR1 the predominant one in these cells. 3α-THP (10nM) increased the expression of TGFβ1, EGFR, VEGF and cyclin D1 genes. P4 increased TGFβ1 and EGFR expression, and this effect was blocked by F. These data provide evidence that P4, through its metabolite 3α-THP, can promote in part cell proliferation of human GBM cells by changing the expression of genes involved in tumor progression.