RESUMO
Objective To study the possible mechanism of in vivo production and congregation of macroprolactinemia (M-PRL) . Methods 50 cases of hyperprolactinemia(HPRL) ,50 cases of M-PRL and 25 healthy persons were selected as the HPRL group , M-PRL group and control group respectively .The chemiluminescence method was adopted to detect the levels of serum hormones and thyroid hormones .Then the detection results were statistically analyzed .Results The levels of serum testosterone ,sex hormone binding globulin(SHBG) ,thyroglobulin antibody and thyroid peroxidase in the M-PRL and HPRL groups were significantly higher than those in the control group .Serum estradiol levels in the M-PRL and HPRL group were lower than those in control group ,the difference was statistically significant (P＜0 .05) .Serum Prog level of the M-PRL group was lower than that of the control group ,the difference was statistically significant (P＜0 .05) .However the levels of serum testosterone ,estradiol ,luteinizing hormone(LH) ,follicle-stimulating hormone(FSH) and SHBG ,and LH/FSH ratio had no statistical difference between the M-PRL group and HPRL group(P＞0 .05) .Conclusion Certain degrees of sex hormones abnormality and autoimmune abnormality may exist in the patients with M-PRL .
RESUMO
Objective To explore the mechanism by which tumor necrosis factor alpha(TNF-α) induces RIP1 kinase-dependented apoptosis in L929-A fibroblastoma cells.Methods The sub-mitochondrial localization of receptor-interacting protein 1(RIP1),caspase-8 and Bid proteins was detected by dose-gradient trypsin digestion and Western blotting.The levels of reactive oxygen species (ROS),intracellular calcium concentration,mitochondrial membrane potential (MMP),and cellular adenosine triphosphate(ATP) content were determined by fluorescent probe labeling and flow cytometry assay.The mitochondrial respiratory chain complex Ⅰ and Ⅲ activities were detected by commercial kits.Nec-1,A RIP1 kinase specific inhibitor,and RIP1-/-or Bid-/-L929-A cells were used to detect the roles of RIP1 kinase and Bid protein in cell death.Results RIP1,caspase-8 and Bid proteins were co-located in the outer membrane of mitochondrial.TNF-α exposure for 3 h could induce Bid cleavage,inhibit mitochondrial respiratory chain complex Ⅲ activity and reduce MMP.Following these changes and after TNF-α exposure for 6-12 h,the intracellular calcium concentration and ROS were increased,whereas the ATP concentration was decreased,and the cells were killed.Inhibiting RIP1 kinase or knockdown RIP1 or Bid protein could suppress all the cytotoxic effects of TNF-α.Conclusion TNF-α treatment can result in RIP1 kinase-mediated Bid cleavage and inhibit mitochondrial respiratory chains and cell energy metabolism,which ultimately leads to the death of L929-A cells.