The STAT5A-mediated induction of pyruvate dehydrogenase kinase 4 expression by prolactin or growth hormone in adipocytes.
The purpose of this study was to determine whether pyruvate dehydrogenase kinase (PDK)4 was expressed in adipocytes and whether PDK4 expression was hormonally regulated in fat cells. Both Northern blot and Western blot analyses were conducted on samples isolated from 3T3-L1 adipocytes after various treatments with prolactin (PRL), growth hormone (GH), and/or insulin. Transfection of PDK4 promoter reporter constructs was performed. In addition, glucose uptake measurements were conducted. Our studies demonstrate that PRL and porcine GH can induce the expression of PDK4 in 3T3-L1 adipocytes. Our studies also show that insulin pretreatment can attenuate the ability of these hormones to induce PDK4 mRNA expression. In addition, we identified a hormone-responsive region in the murine PDK4 promoter and characterized a STAT5 binding site in this region that mediates the PRL (sheep) and GH (porcine) induction in PDK4 expression in 3T3-L1 adipocytes. PDK4 is a STAT5A target gene. PRL is a potent inducer of PDK4 protein levels, results in an inhibition of insulin-stimulated glucose transport in fat cells, and likely contributes to PRL-induced insulin resistance.
White
Ursula A
UA
Department of Biological Sciences, Louisiana State University, Baton Rouge, Louisiana 70803, USA.
Coulter
Ann A
AA
Miles
Tiffany K
TK
Stephens
Jacqueline M
JM
D016475:3T3 Cells; D017667:Adipocytes / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D002467:Cell Nucleus / Q000201:enzymology; D003600:Cytosol / Q000201:enzymology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D017930:Genes, Reporter; D019382:Human Growth Hormone / Q000494:pharmacology*; D051379:Mice; D010957:Plasmids; D011388:Prolactin / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D011494:Protein Kinases / Q000235:genetics*; D050799:STAT5 Transcription Factor / Q000502:physiology*; D014162:Transfection
D050799:STAT5 Transcription Factor; D019382:Human Growth Hormone; D011388:Prolactin; D011494:Protein Kinases; C403287:pyruvate dehydrogenase kinase 4