Glioblastoma cells express crucial enzymes involved in androgen synthesis: 3β‐hydroxysteroid dehydrogenase, 17‐20α‐hydroxylase, 17β‐hydroxysteroid dehydrogenase and 5α‐reductase

Jose Antonio Mondragón; Yesenia Serrano; Andrea Torres; Martin Orozco; José Segovia; Gabriel Manjarrez; Marta Catalina Romano

doi:10.1002/edm2.289

journal article Open Access Jul 23, 2021

Glioblastoma cells express crucial enzymes involved in androgen synthesis: 3β‐hydroxysteroid dehydrogenase, 17‐20α‐hydroxylase, 17β‐hydroxysteroid dehydrogenase and 5α‐reductase

Jose Antonio Mondragón

Yesenia Serrano Andrea Torres Martin Orozco

José Segovia

Gabriel Manjarrez

Marta Catalina Romano

Endocrinology, Diabetes & Metabolism Vol. 4 No. 4 · Wiley

View at Publisher Save 10.1002/edm2.289

Abstract

AbstractGlioblastoma (GB) is the most common and aggressive primary brain tumour in adult humans. Therapeutic resistance and tumour recurrence after surgical removal contribute to poor prognosis for glioblastoma patients. Men are known to be more likely than women to develop an aggressive form of GB, and differences in sex steroids have emerged as a leading explanation for this finding. Studies indicate that the metabolism and proliferation of GB‐derived cells are increased by sex steroids, the expression of androgen receptors (ARs) and the synthesis of androgens and oestrogens, suggesting that these hormones have a role in the tumour pathogenesis. The expression of aromatase, the enzyme that converts androgens to oestrogens, has been reported in glial cells and GB cell lines. Thus, it was necessary to test whether the steroidogenic enzymes involved in androgen synthesis are expressed in GB cells. Therefore, here, we investigated the expression of four key enzymes involved in androgen synthesis in human‐derived GB cells. U87 cells were cultured in Dulbecco's modified Eagle medium plus foetal bovine serum and antibiotics on slides for immunocytochemistry or immunofluorescence. U87, LN229 and C6 cells were also cultured in multi‐well chambers to obtain proteins for Western blotting. We used primary antibodies against 3β‐hydroxysteroid dehydrogenase (3β‐HSD), 17α‐hydroxilase/17,20‐lyase (P450c17), 17β‐hydroxysteroid dehydrogenase (17β‐HSD) and 5α‐reductase. Immunocytochemistry, and immunofluorescence results revealed that glioblastoma cells express 3β‐HSD, P450c17, 17β‐HSD and 5α‐reductase proteins in their cytoplasm. Moreover, Western blot analyses revealed bands corresponding to the molecular weight of these four enzymes in the three GB cell lines. Thus, glioblastoma cells have the key enzymatic machinery necessary to synthesize androgens, and these enzymes might be useful targets for new therapeutic approaches.

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Details

Published: Jul 23, 2021
Vol/Issue: 4(4)
License: View

Authors

J

Jose Antonio Mondragón

Departamento de Fisiología Biofísica y Neurociencias Centro de Investigación y de Estudios Avanzados del IPN Ciudad de Mexico Mexico; Unidad de Enfermedades Neurológicas Hospital de Especialidades México City México

Y

Yesenia Serrano