Effect of hypothyroidism on oxidative stress, p38 and c-Jun N-terminal kinase mRNA expression in testicular mitochondria of male rats / 中华地方病学杂志

ABSTRACT

Objective To define the effect of hypothyroidism on oxidative stress,p38 and c-Jun N-terminal kinases (JNK) mRNA expression in testicular mitochondria of male rats,and to explore the mechanism of hypothyroidism on reproduction.Methods According to body weight (240-270 g),30 male Wistar rats were divided into control group (C group,1 ml/kg normal saline by intragastric administration),low-dose group (L group,0.1 mg/kg propylthiouracil 1 ml/kg by intragastric administration) and high-dose group (H group,10.0 mg/kg propylthiouracil 1 ml/kg by intragastric administration),10 rats in each group,body mass was weighed once every 3 days.After 60 days,all rats were killed.The levels of thyroid hormones [total triiodothyronine (TT3),total thyroxine (TT4),and thyroid stimulating hormone (TSH)] were measured by radioimmunoassay.The activities of superoxide dismutase (SOD) and catalase (CAT) in the testicular mitochondria were determined with spectrophotometric assay.The mRNA expression levels of p38 and JNK in testicular mitochondria were detected by real-time quantitative PCR.Results The weights of H group in 30 and 60 days [(265.73 ± 5.10),(253.72 ± 5.09) g] were significantly decreased in comparison with those of C group [(344.62 ± 4.69),(395.33 ± 8.36) g] and L group [(333.66 ± 3.53),(386.08 ± 7.70) g,P ＜0.05].While,testis organ coefficient of H group [(1.20 ± 0.05) g/100 g] were significantly increased compared with those of L group [(0.93 ± 0.03) g/100 g] and C group [(0.88 ± 0.03) g/100 g,P ＜ 0.05].The serum levels of TT3 [(0.39 ± 0.01) nmol/L] and TT4 [(15.47 ± 1.21) nmol/L] in H group were found to be significantly decreased compared with those of C group [(0.86 ± 0.07),(45.56 ± 1.52) nmol/L] and L group [(0.79 ± 0.06),(39.02 ± 1.33) nmol/L,P ＜ 0.05];whereas the level of TSH [(0.65 ± 0.09) mU/L)] was increased in comparison with those of the C group [(0.18 ± 0.06) mU/L] and L group [(0.27 ± 0.05) mU/L,P ＜ 0.05].In addition,the level of SOD in H group [(60.37 ± 3.14) U/mg prot] was decreased compared with that of C group [(75.18 ± 6.13) U/mg prot,P ＜ 0.05];the level of CAT in H group [(1.46 ± 0.25) U/mg prot] and L group [(1.67 ± 0.39) U/mg prot] decreased significantly compared with that of C group [(3.79 ± 0.44) U/mg prot,P ＜ 0.05].And compared with C (1.000 0 ± 0.000 0) and L (1.114 2 ± 0.124 1) groups,p38 mRNA expression in H group (1.387 4 ± 0.122 0) was significantly increased (P ＜ 0.05).However,there was no significant change in JNK mRNA expression between groups (F =0.95,P ＞ 0.05).Conclusion Hypothyroidism may induce oxidative stress of testicular mitochondria leading to the change of p38 cell signal path and then damage the reproductive system in male rats.