| dc.description.abstract | Adipocytes are now known to express and secrete a variety of bioactive peptides that regulate diabetes, obesity, cancer, and other biomedical diseases at the endocrine levels. Resistin is a cysteine-rich hormone that was first isolated from adipose tissues and found to link obesity to Type 2 diabetes in rodents. The overall objective of this dissertation was thus to examine the regulation and actions of resistin. The first chapter shows that the forkhead transcription factor FOXO1 stimulates the expression of the adipocyte resistin gene via the direct binding of resistin promoter. The second chapter shows that environmental estrogens, such as octylphenol, nonylphenol and bisphenol A, had different effects on resistin gene expression in 3T3-L1 adipocytes. In vivo experiments showed that octylphenol increased resistin expression in epididymal adipose tissue and serum levels of resistin and glucose supports its in vitro effect. Furthermore, this chapter demonstrated that the agonist of the respective estrogen receptor alpha and beta, such as propylpyrazoletriol and diarylpropionitrile, dose- and time-dependently stimulated resistin gene expression in 3T3-L1 adipocytes. The third chapter shows that resistin stimulated the expression of suppressor of cytokine signaling (SOCS) genes, particularly SOCS-1, -2, -3, -4, -5, and -6 but not SOCS-7 and CIS-1 genes, in human PC-3 prostate cancer cell via the toll-like receptor 4 (TLR4), extracellular signal-regulated kinase, phosphatidylinositol 3-kinase, p38 mitogen-activated protein kinase, c-Jun N-terminal kinase, and Janus kinase 2 but not TLR2 pathways. As resistin, FOXO1, and SOCS all function to regulate diabetes, obesity, and cancer, the results of this study may help explain the mechanism through which resistin modulates the processes of these biomedical diseases and environmental hormone-mediated metabolic and reproductive disorders. | en_US |