Display options
Share it on

Biol Sex Differ. 2021 Mar 22;12(1):28. doi: 10.1186/s13293-021-00372-5.

Impact of sex in the prevalence and progression of glioblastomas: the role of gonadal steroid hormones.

Biology of sex differences

Claudia Bello-Alvarez, Ignacio Camacho-Arroyo

Affiliations

  1. Unidad de Investigación en Reproducción Humana, Instituto Nacional de Perinatología-Facultad de Química, Universidad Nacional Autónoma de México (UNAM), 04510, Ciudad de México, México.
  2. Unidad de Investigación en Reproducción Humana, Instituto Nacional de Perinatología-Facultad de Química, Universidad Nacional Autónoma de México (UNAM), 04510, Ciudad de México, México. [email protected].

PMID: 33752729 PMCID: PMC7986260 DOI: 10.1186/s13293-021-00372-5

Abstract

BACKGROUND: As in other types of cancers, sex is an essential factor in the origin and progression of glioblastomas. Research in the field of endocrinology and cancer suggests that gonadal steroid hormones play an important role in the progression and prevalence of glioblastomas. In the present review, we aim to discuss the actions and mechanism triggered by gonadal steroid hormones in glioblastomas.

MAIN BODY: Glioblastoma is the most common malignant primary brain tumor. According to the epidemiological data, glioblastomas are more frequent in men than in women in a 1.6/1 proportion both in children and adults. This evidence, and the knowledge about sex influence over the prevalence of countless diseases, suggest that male gonadal steroid hormones, such as testosterone, promote glioblastomas growth. In contrast, a protective role of female gonadal steroid hormones (estradiol and progesterone) against glioblastomas has been questioned. Several pieces of evidence demonstrate a variety of effects induced by female and male gonadal steroid hormones in glioblastomas. Several studies indicate that pregnancy, a physiological state with the highest progesterone and estradiol levels, accelerates the progression of low-grade astrocytomas to glioblastomas and increases the symptoms associated with these tumors. In vitro studies have demonstrated that progesterone has a dual role in glioblastoma cells: physiological concentrations promote cell proliferation, migration, and invasion while very high doses (out physiological range) reduce cell proliferation and increases cell death.

CONCLUSION: Gonadal steroid hormones can stimulate the progression of glioblastomas through the increase in proliferation, migration, and invasion. However, the effects mentioned above depend on the concentrations of these hormones and the receptor involved in hormone actions. Estradiol and progesterone can exert promoter or protective effects while the role of testosterone has been always associated to glioblastomas progression.

Keywords: Estradiol; Glioblastoma; Prevalence; Progesterone; Progression; Sex differences; Testosterone

References

  1. Biomed Res Int. 2017;2017:1295087 - PubMed
  2. Oncotarget. 2017 Jun 20;8(25):40765-40777 - PubMed
  3. ScientificWorldJournal. 2014;2014:159150 - PubMed
  4. Neuroendocrinology. 1992 Dec;56(6):895-901 - PubMed
  5. J Korean Med Sci. 2004 Feb;19(1):123-6 - PubMed
  6. Anticancer Res. 2014 May;34(5):2385-8 - PubMed
  7. J Steroid Biochem Mol Biol. 2009 Jan;113(1-2):80-4 - PubMed
  8. J Neurooncol. 2018 Apr;137(2):357-365 - PubMed
  9. J Cancer Res Clin Oncol. 2004 Jul;130(7):405-10 - PubMed
  10. Cancer Epidemiol Biomarkers Prev. 2010 Oct;19(10):2421-7 - PubMed
  11. J Neuroendocrinol. 2006 Aug;18(8):621-8 - PubMed
  12. Cancer Causes Control. 2011 May;22(5):697-714 - PubMed
  13. Neurosurgery. 1995 Sep;37(3):496-503; discussion 503-4 - PubMed
  14. J Neurooncol. 2014 Jun;118(2):297-304 - PubMed
  15. Am J Epidemiol. 2006 Oct 1;164(7):629-36 - PubMed
  16. Cancer Epidemiol. 2014 Jun;38(3):291-7 - PubMed
  17. Cancer Cell. 2016 May 9;29(5):711-722 - PubMed
  18. Cancer Cell. 2010 Jan 19;17(1):98-110 - PubMed
  19. Steroids. 2016 Jan;105:19-25 - PubMed
  20. J Steroid Biochem Mol Biol. 2012 Oct;132(1-2):127-34 - PubMed
  21. Arch Med Res. 2016 Aug;47(6):419-426 - PubMed
  22. Cancer Epidemiol Biomarkers Prev. 1999 Feb;8(2):189-94 - PubMed
  23. J Neurooncol. 2006 Mar;77(1):17-23 - PubMed
  24. Arch Med Res. 2019 May;50(4):187-196 - PubMed
  25. Oncotarget. 2018 Apr 13;9(28):19980-19993 - PubMed
  26. J Korean Med Sci. 1996 Dec;11(6):517-21 - PubMed
  27. Cancer. 1997 Dec 1;80(11):2133-40 - PubMed
  28. Mol Cancer Ther. 2020 Oct;19(10):2163-2174 - PubMed
  29. Cancer Res. 2004 Jan 1;64(1):423-8 - PubMed
  30. J Steroid Biochem Mol Biol. 2015 Feb;146:62-73 - PubMed
  31. Oncotarget. 2017 Apr 4;8(14):23142-23154 - PubMed
  32. Nat Rev Genet. 2008 Dec;9(12):911-22 - PubMed
  33. Endocrine. 2007 Oct;32(2):129-35 - PubMed
  34. Brain Res Bull. 2001 Sep 1;56(1):43-8 - PubMed
  35. CNS Neurosci Ther. 2016 May;22(5):342-50 - PubMed
  36. J Steroid Biochem Mol Biol. 2015 Nov;154:176-85 - PubMed
  37. Brain Res Mol Brain Res. 2002 Jun 30;103(1-2):1-11 - PubMed
  38. Cancer Med. 2020 Aug;9(16):5767-5780 - PubMed
  39. Am J Hematol. 2016 Dec;91(12):1215-1220 - PubMed
  40. Clin Neurol Neurosurg. 2018 Oct;173:20-30 - PubMed
  41. J Neurooncol. 2020 May;147(3):567-575 - PubMed
  42. Sci Transl Med. 2019 Jan 2;11(473): - PubMed
  43. Biomed Res Int. 2016;2016:8065830 - PubMed
  44. Mol Cell Endocrinol. 2016 Oct 15;434:166-75 - PubMed
  45. J Steroid Biochem Mol Biol. 2014 Oct;144 Pt B:463-70 - PubMed
  46. Anim Reprod Sci. 2018 Jan;188:123-129 - PubMed
  47. Cell Mol Neurobiol. 2014 May;34(4):479-89 - PubMed
  48. Neuroscience. 2006;138(3):957-65 - PubMed
  49. PLoS One. 2013 Jul 16;8(7):e68695 - PubMed
  50. Endocrinology. 2008 Feb;149(2):534-43 - PubMed
  51. Am J Pathol. 2007 May;170(5):1445-53 - PubMed
  52. Lancet Oncol. 2008 Apr;9(4):385-91 - PubMed
  53. J Neurosurg. 2018 Jan;128(1):3-13 - PubMed
  54. Biol Sex Differ. 2012 Jan 25;3:3 - PubMed
  55. Mol Cell Biochem. 2014 Oct;395(1-2):99-107 - PubMed
  56. Neurosurg Rev. 2019 Jun;42(2):351-369 - PubMed
  57. Brain Res. 2013 Mar 29;1503:97-107 - PubMed
  58. Onco Targets Ther. 2020 Sep 03;13:8813-8823 - PubMed
  59. Neuro Oncol. 2018 Oct 1;20(suppl_4):iv1-iv86 - PubMed
  60. Neuroendocrinology. 2009;90(1):73-81 - PubMed
  61. PLoS One. 2015 Jun 25;10(6):e0131441 - PubMed
  62. J Clin Endocrinol Metab. 2001 Feb;86(2):818-27 - PubMed
  63. EPMA J. 2016 Nov 10;7:22 - PubMed
  64. PLoS One. 2015 Oct 20;10(10):e0140257 - PubMed
  65. Steroids. 2017 Mar;119:36-42 - PubMed
  66. J Neurosurg. 1990 Nov;73(5):736-42 - PubMed
  67. J Cancer Res Clin Oncol. 2019 Sep;145(9):2293-2301 - PubMed
  68. J Clin Invest. 2014 Sep;124(9):4123-33 - PubMed
  69. Br J Clin Pharmacol. 2015 Apr;79(4):677-84 - PubMed
  70. Otolaryngol Head Neck Surg. 2018 Oct;159(4):717-723 - PubMed
  71. Cancer. 1990 May 1;65(9):1968-70 - PubMed
  72. Mol Cancer Ther. 2012 May;11(5):1174-82 - PubMed
  73. Mol Cell Endocrinol. 2018 Dec 5;477:81-89 - PubMed
  74. Med Hypotheses. 2001 Sep;57(3):337-43 - PubMed
  75. Neuroscience. 2015 Feb 12;286:162-70 - PubMed
  76. Nat Genet. 2017 Jan;49(1):10-16 - PubMed
  77. Biochim Biophys Acta. 2012 Feb;1823(2):379-86 - PubMed
  78. Horm Cancer. 2020 Apr;11(2):117-127 - PubMed
  79. Int J Oncol. 2010 May;36(5):1067-80 - PubMed
  80. Clin Neuropharmacol. 1984;7(4):347-50 - PubMed
  81. Life Sci. 2020 May 15;249:117536 - PubMed
  82. Tumour Biol. 2015 Feb;36(2):967-72 - PubMed
  83. Neuroscience. 1999 Mar;89(2):567-78 - PubMed
  84. Steroids. 2020 Nov;163:108708 - PubMed
  85. Neuroscience. 2006 Sep 15;141(4):1793-800 - PubMed
  86. Eur J Orthop Surg Traumatol. 2019 Jan;29(1):9-15 - PubMed
  87. Cell Mol Life Sci. 2015 Sep;72(17):3323-42 - PubMed
  88. Brain Res. 2008 May 13;1209:115-27 - PubMed
  89. Cancer Genomics Proteomics. 2016 May-Jun;13(3):219-30 - PubMed
  90. Biol Sex Differ. 2020 Apr 15;11(1):17 - PubMed
  91. Cell Stem Cell. 2017 Feb 2;20(2):233-246.e7 - PubMed
  92. J Neurosurg. 1999 Jun;90(6):1072-7 - PubMed
  93. Mol Endocrinol. 2013 Apr;27(4):693-702 - PubMed
  94. Biomed Res Int. 2014;2014:393174 - PubMed
  95. Neuroendocrinology. 2012;96(1):41-50 - PubMed
  96. J Neurooncol. 2014 Sep;119(2):275-84 - PubMed
  97. Sci Rep. 2019 Jan 30;9(1):988 - PubMed
  98. Acta Neuropathol Commun. 2018 Feb 20;6(1):12 - PubMed
  99. BMB Rep. 2016 Sep;49(9):488-96 - PubMed
  100. Acta Neuropathol. 2016 Jun;131(6):803-20 - PubMed
  101. Steroids. 2020 Mar;155:108556 - PubMed
  102. J Comp Neurol. 2000 Sep 25;425(3):422-35 - PubMed
  103. PLoS Genet. 2008 Jun 20;4(6):e1000100 - PubMed
  104. Cancer Lett. 2020 Jan 1;468:41-47 - PubMed
  105. Front Endocrinol (Lausanne). 2019 Feb 04;10:16 - PubMed
  106. J Obstet Gynaecol Res. 2016 Oct;42(10):1385-1389 - PubMed
  107. J Neurosci. 2004 Jun 30;24(26):5913-21 - PubMed
  108. N Engl J Med. 2005 Mar 10;352(10):987-96 - PubMed

Publication Types