Valproic acid (VPA), an antiepileptic and mood stabilizer, modulates neurotransmission and gene expression by inhibiting histone deacetylase activity. It is reported that VPA may affects the steroid hormone level. In this study, VPA-induced acute metabolic alterations were investigated using liquid chromatography-tandem mass spectrometry in prepubertal mice brain. In VPA-treated (400 mg/kg in saline solution, intraperitoneal) mice, cortisol levels were increased (female: P < 0.004, male: P < 0.003) and 17β-estradiol levels were decreased (Both P < 0.03). Furthermore, in the VPA-treated male mice, dihydrotestosterone levels were increased (P < 0.02) and testosterone were decreased (P < 0.002). The 4-hydroxylase activity was upregulated in the female VPA-treated mice (P < 0.01) and the 5α-reductase activity was increased in the male VPA-treated mice (P < 0.003). These results indicate sex specific differences in VPA-induced steroid metabolism in the brain cortex.

丙戊酸（VPA）是一种抗癫痫药和情绪稳定剂，通过抑制组蛋白脱乙酰基酶活性来调节神经传递和基因表达。据报道，VPA可能会影响类固醇激素水平。在这项研究中，使用液相色谱-串联质谱法在青春期前小鼠大脑中研究了VPA诱导的急性代谢改变。在接受VPA治疗的小鼠（腹膜内盐水溶液，400 mg / kg）中，皮质醇水平升高（雌性：P  <0.004，雄性：P  <0.003），而17β-雌二醇水平降低（均P  <0.03）。此外，在接受VPA处理的雄性小鼠中，二氢 睾丸激素水平升高（P <0.02），睾丸激素水平降低（P <0.002）。在雌性VPA处理的小鼠中4-羟化酶活性上调（P  <0.01），在雄性VPA处理的小鼠中5α-还原酶活性增加（P  <0.003）。这些结果表明，VPA诱导的大脑皮质类固醇代谢中存在性别特异性差异。