Identifier

etd-11112008-175227

Degree

Master of Science (MS)

Department

Biological Sciences

Document Type

Thesis

Abstract

Adiponectin is a hormone secreted from adipocytes that plays an important role in insulin sensitivity and fatty acid oxidation. The secretion of adiponectin from adipose tissue has been shown to be attenuated by treatment with prolactin (PRL). PRL is a potent STAT5 activator, and studies have indicated that it can modulate the expression of several genes in adipocytes. In this study, we demonstrate that 3T3-L1 adipocytes treated with PRL exhibit a reduction in adiponectin levels. Furthermore, we identified three putative STAT5 binding sites in the mouse adiponectin promoter and show that only one of these, located at -3809, binds nuclear protein in a PRL dependent manner. Mutation of the STAT5 binding site abrogated PRL dependent protein binding, and supershift analysis revealed that STAT5A and 5B, but not STATs 1 and 3, bind to this site in response to PRL. Promoter/reporter constructs containing the -3809 site were found to be responsive to PRL. Taken together, these data strongly suggest that PRL regulates adiponectin transcription through the binding of STAT5 to the -3809 site.

Date

2008

Document Availability at the Time of Submission

Release the entire work immediately for access worldwide.

Committee Chair

Stephens Jacqueline

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