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The effect of finasteride and dutasteride on the synthesis of neurosteroids by glioblastoma cells.
Steroids. 2019 Dec 20; 155:108556.S

Abstract

Glioblastoma (GBM) is the most aggressive local brain tumor and effective treatments are lacking. Many studies have proposed an important participation of steroid hormones in the development of gliomas. Evidence was provided by statistics analysis where the incidence in adult population is 50% higher in men than in women. Female patients have a better prognosis for survival compared to male patients with GBM. Also, the expression of receptors to estrogen, progesterone and androgens in glioma cell lines and tumor biopsies, and glucocorticoid receptors in GBM cell lines had been reported. Here we have investigated the effect of the pharmacological inhibition of 5-α reductases on the capacity of GBM derived cell lines C6 (rat) and U87 (human) to synthesize neurosteroids. As the knowledge of the pathways used to synthesize neurosteroids by GBM derived cells was incomplete, we have investigated the synthesis of these steroids by C6 and U87 cells using tritiated precursors and thin layer chromatography (TLC). Increasing concentrations of finasteride and dutasteride were added to U87 culture media that was collected after 24 and 48 h. The results of the study showed that C6 cells incubated with 3H-cholesterol yielded dihydroandrosterone, hydroxytestosterone, androstenediol, androstenedione and estriol, while U87 cells also synthesized progesterone, and androstanedione. Incubation with 3H-androstenedione or 3H-testosterone mainly yielded dihydrotestosterone, androsterone, dihydroandrosterone, hydroxytestosterone, and estradiol in both lines. To note, we showed here for the first time that U87 cells synthesize corticosteroids. Addition of finasteride or dutasteride to U87 cells reduced androgen and estrogen synthesis. Dutasteride also decreased the synthesis of dihydrocorticosterone and allotetrahydrodesoxycorticosterone while deoxycorticosterone was accumulated. In summary, both GBM cell lines synthesize numerous neurosteroids, including 5-α reductase products and 3α-HSD pathways that were inhibited by finasteride and dutasteride. These inhibitors may be considered as tools to control neurosteroid synthesis of potential relevance for GBM survival.

Authors+Show Affiliations

Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados del IPN, Avenida IPN # 2508, Ciudad de Mexico 07360, Mexico.Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados del IPN, Avenida IPN # 2508, Ciudad de Mexico 07360, Mexico.Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados del IPN, Avenida IPN # 2508, Ciudad de Mexico 07360, Mexico.Departamento de Sistemas Biológicos, Universidad Autónoma Metropolitana-Xochimilco, Ciudad de México, Mexico.Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados del IPN, Avenida IPN # 2508, Ciudad de Mexico 07360, Mexico.Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados del IPN, Avenida IPN # 2508, Ciudad de Mexico 07360, Mexico. Electronic address: mromano@fisio.cinvestav.mx.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31866547

Citation

Pinacho-Garcia, Luis Manuel, et al. "The Effect of Finasteride and Dutasteride On the Synthesis of Neurosteroids By Glioblastoma Cells." Steroids, vol. 155, 2019, p. 108556.
Pinacho-Garcia LM, Valdez RA, Navarrete A, et al. The effect of finasteride and dutasteride on the synthesis of neurosteroids by glioblastoma cells. Steroids. 2019;155:108556.
Pinacho-Garcia, L. M., Valdez, R. A., Navarrete, A., Cabeza, M., Segovia, J., & Romano, M. C. (2019). The effect of finasteride and dutasteride on the synthesis of neurosteroids by glioblastoma cells. Steroids, 155, 108556. https://doi.org/10.1016/j.steroids.2019.108556
Pinacho-Garcia LM, et al. The Effect of Finasteride and Dutasteride On the Synthesis of Neurosteroids By Glioblastoma Cells. Steroids. 2019 Dec 20;155:108556. PubMed PMID: 31866547.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The effect of finasteride and dutasteride on the synthesis of neurosteroids by glioblastoma cells. AU - Pinacho-Garcia,Luis Manuel, AU - Valdez,Ricardo A, AU - Navarrete,Araceli, AU - Cabeza,Marisa, AU - Segovia,José, AU - Romano,Marta C, Y1 - 2019/12/20/ PY - 2019/09/21/received PY - 2019/12/08/accepted PY - 2019/12/24/pubmed PY - 2019/12/24/medline PY - 2019/12/24/entrez KW - Dutasteride KW - Finasteride KW - Glioblastoma KW - Steroids synthesis SP - 108556 EP - 108556 JF - Steroids JO - Steroids VL - 155 N2 - Glioblastoma (GBM) is the most aggressive local brain tumor and effective treatments are lacking. Many studies have proposed an important participation of steroid hormones in the development of gliomas. Evidence was provided by statistics analysis where the incidence in adult population is 50% higher in men than in women. Female patients have a better prognosis for survival compared to male patients with GBM. Also, the expression of receptors to estrogen, progesterone and androgens in glioma cell lines and tumor biopsies, and glucocorticoid receptors in GBM cell lines had been reported. Here we have investigated the effect of the pharmacological inhibition of 5-α reductases on the capacity of GBM derived cell lines C6 (rat) and U87 (human) to synthesize neurosteroids. As the knowledge of the pathways used to synthesize neurosteroids by GBM derived cells was incomplete, we have investigated the synthesis of these steroids by C6 and U87 cells using tritiated precursors and thin layer chromatography (TLC). Increasing concentrations of finasteride and dutasteride were added to U87 culture media that was collected after 24 and 48 h. The results of the study showed that C6 cells incubated with 3H-cholesterol yielded dihydroandrosterone, hydroxytestosterone, androstenediol, androstenedione and estriol, while U87 cells also synthesized progesterone, and androstanedione. Incubation with 3H-androstenedione or 3H-testosterone mainly yielded dihydrotestosterone, androsterone, dihydroandrosterone, hydroxytestosterone, and estradiol in both lines. To note, we showed here for the first time that U87 cells synthesize corticosteroids. Addition of finasteride or dutasteride to U87 cells reduced androgen and estrogen synthesis. Dutasteride also decreased the synthesis of dihydrocorticosterone and allotetrahydrodesoxycorticosterone while deoxycorticosterone was accumulated. In summary, both GBM cell lines synthesize numerous neurosteroids, including 5-α reductase products and 3α-HSD pathways that were inhibited by finasteride and dutasteride. These inhibitors may be considered as tools to control neurosteroid synthesis of potential relevance for GBM survival. SN - 1878-5867 UR - https://www.unboundmedicine.com/medline/citation/31866547/The_effect_of_finasteride_and_dutasteride_on_the_synthesis_of_neurosteroids_by_glioblastoma_cells L2 - https://linkinghub.elsevier.com/retrieve/pii/S0039-128X(19)30246-6 DB - PRIME DP - Unbound Medicine ER -
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