Wei sheng yan jiu = Journal of hygiene research · 2015
[Testicular oxidative stress and downregulation of CYP17a1 indused by di (n-butyl) phthalate inhibit synthesis of testosterone].
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Yu Miao, Zhang Linyuan, Qiao Peihuan, Chang Bing
Аннотация
OBJECTIVE: To explore the relationship and possible mechanisms between testicular oxidative injury caused by DBP and the testosterone synthesis pathway.
METHODS: Twenty-four male Wistar male rats (4-wk-old) were randomly divided into 4 groups, three doses of DBP (80, 200 and 500 mg/kg) groups and a vehicle (corn oil) control group, 6 animals each. The rats were respectively administered by gavage once a day for four weeks. They were sacrificed after 4 weeks treatment and the body weights, testis, epididymis were weighed, respectively. The oxidation of MDA and ROS, the activity changes of antioxidases SOD, CAT and GPx-1, as well as the activities of steroid synthetases 3β-HSD1, 17β-HSD3 in the testis homogenate were measured by biochemical methods. The levels of testosterone, LH, FSH in peripheral blood and testosterone, ASD in testis were measured by radioimmunoassay. The intensities of expresses of StAR, P450scc, 3β-HSD1, 17β-HSD3 and CYP17a1 mRNA were detected by real-time qPCR.
RESULTS: In 500 mg/kg dose group, the body weights and weigths of testis were decreased obviously (P < 0.05). The concentration of serum LH and FSH was increased, the consentration of serum T, testicular T and testicular ASD was decreased (P < 0.05). The oxidation of MDA and ROS was increased distinctly and the activities of SOD, CAT, GPx-1 and 3β-HSD1 were reduced (P < 0.05). StAR, P450scc, 3β-HSD1 and CYP17a1 mRNA were decreased, 17β-HSD3 mRNA was increased (P < 0.05). In 200 mg/kg dose groups, LH, FSH level in peripheral blood were increased and ASD level in testis was decreased (P < 0.05). The oxidation of ROS was increased and activity of GPx-1 and 3β- HSD1 were decreased (P < 0.05). StAR, P450scc and CYP17a1 mRNA were decreased (P < 0.05). There were no changes in 80 mg/kg group.
CONCLUSION: DBP exposure disturbed the balances of oxidation/antioxidation, then result in the decline of GPx-1 activity, CYP17a1 mRNA and ASD level which caused the decrease of testosterone synthesis in leydig cell. It is speculated that the decrease of CYP17a1 may be one of the mechanisms of toxic effects of DBP.
METHODS: Twenty-four male Wistar male rats (4-wk-old) were randomly divided into 4 groups, three doses of DBP (80, 200 and 500 mg/kg) groups and a vehicle (corn oil) control group, 6 animals each. The rats were respectively administered by gavage once a day for four weeks. They were sacrificed after 4 weeks treatment and the body weights, testis, epididymis were weighed, respectively. The oxidation of MDA and ROS, the activity changes of antioxidases SOD, CAT and GPx-1, as well as the activities of steroid synthetases 3β-HSD1, 17β-HSD3 in the testis homogenate were measured by biochemical methods. The levels of testosterone, LH, FSH in peripheral blood and testosterone, ASD in testis were measured by radioimmunoassay. The intensities of expresses of StAR, P450scc, 3β-HSD1, 17β-HSD3 and CYP17a1 mRNA were detected by real-time qPCR.
RESULTS: In 500 mg/kg dose group, the body weights and weigths of testis were decreased obviously (P < 0.05). The concentration of serum LH and FSH was increased, the consentration of serum T, testicular T and testicular ASD was decreased (P < 0.05). The oxidation of MDA and ROS was increased distinctly and the activities of SOD, CAT, GPx-1 and 3β-HSD1 were reduced (P < 0.05). StAR, P450scc, 3β-HSD1 and CYP17a1 mRNA were decreased, 17β-HSD3 mRNA was increased (P < 0.05). In 200 mg/kg dose groups, LH, FSH level in peripheral blood were increased and ASD level in testis was decreased (P < 0.05). The oxidation of ROS was increased and activity of GPx-1 and 3β- HSD1 were decreased (P < 0.05). StAR, P450scc and CYP17a1 mRNA were decreased (P < 0.05). There were no changes in 80 mg/kg group.
CONCLUSION: DBP exposure disturbed the balances of oxidation/antioxidation, then result in the decline of GPx-1 activity, CYP17a1 mRNA and ASD level which caused the decrease of testosterone synthesis in leydig cell. It is speculated that the decrease of CYP17a1 may be one of the mechanisms of toxic effects of DBP.