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The role of sexual steroid hormones in glioblastoma

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Resumo:Introduction: Glioblastoma (GBM) represents about 30-40% of the Central Nervous System tumors and has 50% more incidence in men than in women. This sex biased pattern suggests that sex hormones may be of relevance for GBM’s etiopathology. However, this hypothesis has not been the target of much investigation so far. Objectives: The aim of this project was to assess the role of sex steroid hormones, estradiol (E2), progesterone (P4), dihydrotestosterone (DHT) and testosterone (T) in cell viability and apoptosis of three GBM cell lines (U-87MG, SNB19 and U-373MG),which represent different grades of GBM aggressiveness, and in a human astrocyte cell line (HASTR/ci35). Materials and methods: The presence of estrogen, progesterone and androgen receptors (ER, PR and AR, respectively) was assessed in U-87MG, SNB19, U-373MG and in HASTR/ci35 by immunocytochemistry. Then, the effect of E2, P4, DHT and T on cell viability was assessed by the 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay upon incubations with physiological concentrations of hormones, during different incubation periods. Results: We found ERα and ERβ expression in HASTR/ci35, U-87MG, SNB19, and U- 373MG. ERα had a predominant cytoplasmatic distribution in all the cells lines except in U-87MG. PR had a marked expression in the U-87MG cell line but not in HASTR/ci35, SNB19 and U-373MG. AR expression was confirmed in all cell lines analysed. E2 increased the viability of HASTR/ci35 and diminished it in SNB19, pointing to a protective role in these lines. Progesterone diminished viability in U-87MG cells but had the opposite effect in the most aggressive cell lines SNB19 and U-373MG. DHT increased the viability of U-87MG, SNB19 and U-373MG. Interestingly, testosterone increased the viability of astrocytes but diminished the viability of U-87MG cells, what contradicts previous studies pointing to its effect in promoting migration, invasion and proliferation in GBM. Conclusion: This study sets the basis for further exploring the effect of these hormones on relevant parameters of cancer such as proliferation, apoptosis, migration and invasion to further elucidate the differences observed in the effect of these hormones on cell viability, that concur with a protective effect of E2 and T, and a more controversial role of P4 in GBM cell lines. On the other hand, DHT, enhanced cell viability, what is a preliminary indication that the higher prevalence of GBM in men might be indeed favoured by their hormonal background.
Autores principais:Oliveira, Mariana Cristina Lança de
Assunto:Glioblastoma Hormonas esteroides sexuais Estradiol Progesterona Testosterona Dihidrotestosterona
Ano:2020
País:Portugal
Tipo de documento:dissertação de mestrado
Tipo de acesso:acesso aberto
Instituição associada:Universidade de Lisboa
Idioma:inglês
Origem:Repositório da Universidade de Lisboa

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