title: Allopregnanolone promotes proliferation and differential gene expression in human glioblastoma cells.
abstract: 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 P4favors 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 P4and 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. P4increased 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.
authors.affiliation: Unidad de Investigación en Reproducción Humana, Instituto Nacional de Perinatología-Facultad de Química, Universidad Nacional Autónoma de México (UNAM), Mexico.
authors.forename: Carmen J
authors.initials: CJ
authors.lastname: Zamora-Sánchez
authors.affiliation: Facultad de Química, Departamento de Biología, UNAM, Mexico.
authors.forename: Valeria
authors.initials: V
authors.lastname: Hansberg-Pastor
authors.affiliation: Instituto Nacional de Medicina Genómica, Ciudad de México, Mexico.
authors.forename: Ivan
authors.initials: I
authors.lastname: Salido-Guadarrama
authors.affiliation: Instituto Nacional de Medicina Genómica, Ciudad de México, Mexico.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Rodríguez-Dorantes
authors.affiliation: Unidad de Investigación en Reproducción Humana, Instituto Nacional de Perinatología-Facultad de Química, Universidad Nacional Autónoma de México (UNAM), Mexico. Electronic address: camachoarroyo@gmail.com.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Camacho-Arroyo
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D042944:Cholestenone 5 alpha-Reductase / Q000378:metabolism; D019938:Cyclin D1 / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D005909:Glioblastoma / Q000378:metabolism*; D006801:Humans; D011280:Pregnanolone / Q000494:pharmacology*; D011374:Progesterone / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; D019938:Cyclin D1; D011374:Progesterone; D011280:Pregnanolone; D042944:Cholestenone 5 alpha-Reductase; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: 5α-Reductase; Allopregnanolone; Allopregnanolone (PubChem CID: 92787); Finasteride (PubChem CID: 57363); Glioblastomas; Human astrocytomas; Mifepristone (PubChem CID: 55245); Progesterone; Progesterone (PubChem CID: 5994); Proliferation