Glioblastoma (GB) is the most aggressive primary brain tumor, the survival rate is low because of a high prevalence of recidives. The incidence of GB in the adult population is 50% higher in men than in women, which suggest a role of steroid hormones in it is development. Information on GB as a steroidogenic tissue is poor. The objectives of this study were: 1, to investigate the capacity of a human GB cell line to synthesize sex steroids and corticosteroid metabolites, and 2, to know the effects of two enzymatic inhibitors of 5-alpha reductase, finasteride and dutasteride, on the hormonal metabolism of the tumoral cells. U87GB cells line were cultured with DMEM, antibiotics and 10% FBS. Thereafter media were replaced by fresh culture media without FBS. Tritiated steroid precursors, progesterone (3H-P4) or androstenedione (3H-A4), were added to the media and cells cultured in the presence or absence of three concentrations of finasteride or dutasteride. Culture media were collected after 24 or 48 h, and extracted with ether. The resulting steroids were separated by thin layer chromatography (TLC). Data were expressed as percent transformation of the tritiated precursors±S.E. Results showed that the U87 cells incubated with 3H-A4, synthesized significant quantities of testosterone after 24 h. The synthesis decreased by 48 h, but the production of its metabolites, dehidrotestosterone (DHT) and androsterone increased. After 48 h finasteride inhibited the production of DHT, dehidro-androsterone (DHA), androsterone and androstanedione. After 48h of culture dutasteride significantly inhibited the synthesis of the testosterone metabolites DHT, DHA, androsterone and androstanedione. The incubation of U87 cells with 3H-P4 for 24 and 48 h lead to the time-dependent synthesis of the corticosteroid metabolites 17-hydroxyprogesterone (17-OHP4), deoxycortisol (DCLS), deoxycorticosterone (DOC), cortisol (CLS), corticosterone (CNE) and aldosterone. The addition of dutasteride to the culture media caused the inhibition of the synthesis of CLS, DCLS, aldosterone, allocorticosterone, and dehidrocorticosterone (DHC) with a significant accumulation of DOC after 48h of culture. In conclusion, U87 cells have the capacity to synthesize sex steroid hormones and corticosteroids, with a remarkable abundance of androgens. 5-alpha reductase inhibitors significantly reduced the synthesis of androgenic metabolites. In addition, dutasteride blocked the 5-alpha reductase action on the corticosteroid pathway, affecting the metabolite synthesis. Therefore, 5-alpha reductase inhibitors may possibly have a role in the control of GB.
Supported by Conacyt Fronteras 2015-2 1256. M. Pinacho receives a Conacyt PhD scholarship.
19 - 22 May 2018
European Society of Endocrinology