Acute Valproate Exposure Induces Sex-Specific Changes in Steroid Hormone Metabolism in the Cerebral Cortex of Juvenile Mice

Abstract

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.

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All data and materials are available upon requests.

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Funding

This work was supported by both the National Research Foundation of Korea(NRF) funded by the Ministry of Education (Grant No. 2017R1D1A3B03033533) and Korea Research Institute of Chemical Technology (Grant No. KK1807-C32 and SI1805-01).

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Correspondence to Soon Ae Kim.

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Cho, S., Chai, J.H., Chang, S. et al. Acute Valproate Exposure Induces Sex-Specific Changes in Steroid Hormone Metabolism in the Cerebral Cortex of Juvenile Mice. Neurochem Res (2020). https://doi.org/10.1007/s11064-020-03065-4

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Keywords

  • Valproic acid (VPA)
  • Steroid hormone
  • Metabolic alteration
  • Sex differences