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

Table 1 Effects of low and high concentrations of P4 on glioblastoma cells in in vitro and in vivo models

P4
Low doses	High doses
• In vitro effects	• In vitro effects
- Induces proliferation through PR actions (10 nM) (ref [8])	- Decreases cell viability (20–80 μM) (ref [9])
- Increases the expression of EGFR and cyclin D1 through its PR and the recruitment of steroid receptor coactivator-1 (SRC-1) (10 nM) (ref [10])	- Enhances toxicity of TMZ (5 and 80 μM) (ref [11])
- Induces the expression of progesterone-induced blocking factor (PIBF) (10 nM) (ref [12])	- Changes in detoxification mechanisms, stress, immune response, and glucose metabolism (100 and 300 μM) (ref [13])
- Stimulates the unphosphorylated state of cofilin (10 nM) (ref [14])	- Reduction of glycolytic metabolism by decreasing the Glut1 expression (8 and 100 μM) (ref [15])
- Induces migration and invasion through PR actions (10 nM) (ref [14])
- Increases the number of glioma stem cells from U251 cells (10 nM) (ref [16])
- Allopregnanolone and 5alpha-dihydroprogesterone (P4 metabolites) increase the number of glioblastoma cells (10 nM) (refs [17, 18])
- 5alpha-dihydroprogesterone increases the migration of glioblastoma cells (10 nM) (ref [18])
• In vivo effects	• In vivo effects
- Increases the area and infiltration of tumor through PR actions (1 mg) (refs [8, 19, 20])	- Reduction of tumor volume (8 and 100 μM) (ref [9]) (100 and 200 μM) (ref [15])
	- Induction of cell senescence by attenuating the signaling pathway PI3K/Akt/mTOR (8 and 100 μM) (ref [9])

ISSN: 2042-6410