STAT 5 proteins are latent transcription factors which have been shown to be activatcd by growth hormone (GH) in many cell types. However, some recent studies also suggest that STAT 513 is a physiological substrate of the insulin receptor. In our studies, we have shown that physiological levels of insulin do not induce STAT 5 tyrosine phosphorylation or affect the nuclear distribution of STATs 5A or 513 in 3T3-L1 adipocytes. Moreover, we did not observe the activation of STAT 5 in the adipose tissue or skeletal muscle of mice following an acute intraperitoneal injection of insulin. However, acute GH administration, both in vitro and in vivo, resulted in the activation of STAT 5 proteins. In summary, our results indicate that STAT 5 proteins are not activated by physiological levels of insulin in adipose tissue. (C) 2003 Elsevier Science (USA). All rights reserved.