Sex-specific Changes in Brain Estrogen Metabolism Induced by Acute Trimethyltin Exposure

Abstract

Background/aim: In this study, we investigated sex-specific effects of acute exposure to trimethyltin, a known neurotoxicant on metabolic steroids.

Materials and methods: We administered intraperitoneally 2.3 mg/kg trimethyltin to 4-week-old male mice and measured the levels of metabolic steroids 24 h after treatment. We also measured mRNA and protein levels of cytochrome P450 1B1 using real-time polymerase chain reaction and western blotting.

Results: Cortisol levels in the cortex increased in both sexes following acute trimethyltin exposure. The estradiol levels decreased, and the 4-hydroxyestradiol levels increased only in females. We also observed increased cytochrome P450 1B1 mRNA and protein levels only in the female cortex.

Conclusion: Acute trimethyltin exposure induces distinct sex-specific metabolic changes in the brain before significant sexual maturation.

Keywords: Trimethyltin; estrogen; mitochondria; sex difference.

Figure 1. Changes in brain metabolic steroid levels in male and female mice brains. A. Cortisol levels in male (left, n=10) and female (n=9) mice brains. B. Estradiol levels in male (left, n=10). C. Estradiol (left, n=9) and 4-OH estradiol levels (right, vehicle, n=9, TMT, n = 10) in female mice brains. Steroid levels were measured by LC-MS/MS analysis. *p<0.05, **p<0.01, ***p<0.001.

Figure 2. Changes in CYP1B1 expression in male and female mice brains. A. Relative expressions of CYP1B1 mRNA measured by RT-PCR in male (left, n=10) and female (right, n=8) mice brains. B. Representative western blots (left). Quantification of CYP1B1 protein levels in male (n=) and female (n=8) mice brains (right). *p<0.05.