GH inhibits primary rat preadipocyte differentiation and expression of late genes required for terminal differentiation. Here we show that GH-mediated inhibition of fatty acid-binding protein aP2 gene expression correlates with the activation of the Janus kinase-2/signal transducer and activator of transcription (STAT)-5 signalling pathway. Within minutes of treatment, GH induced the tyrosine phosphorylation, nuclear localization and DNA binding of STAT5. Importantly, there was no evidence that STAT5 acted via an interaction with peroxisome proliferator-activated receptor gamma. To further understand the mechanism of STAT5 action, we reconstituted the inhibition of aP2 in a non-adipogenic cell line. Using this system, we showed that the ability of GH to inhibit a 520 bp aP2 reporter was largely dependent upon the presence of either STAT5A or STAT5B. Mutant analysis confirmed that the tyrosine phosphorylation of STAT5 was essential for this signalling. However, STAT5's C-terminal transactivation domain was fully dispensable for this inhibition. Taken together, these data confirm a key regulatory role of STAT5 in adipose tIssue and point to STAT5 as the repressing modulator of GH-mediated inhibition in primary preadipocytes.

This article has been cited by other articles:

				Z. E. Floyd, B. M. Segura, F. He, and J. M. Stephens Degradation of STAT5 proteins in 3T3-L1 adipocytes is induced by TNF-{alpha} and cycloheximide in a manner independent of STAT5A activation Am J Physiol Endocrinol Metab, February 1, 2007; 292(2): E461 - E468. [Abstract] [Full Text] [PDF]

				M. Kawai, N. Namba, S. Mushiake, Y. Etani, R. Nishimura, M. Makishima, and K. Ozono Growth hormone stimulates adipogenesis of 3T3-L1 cells through activation of the Stat5A/5B-PPAR{gamma} pathway J. Mol. Endocrinol., January 1, 2007; 38(1): 19 - 34. [Abstract] [Full Text] [PDF]

				J. C. Hogan and J. M. Stephens The Regulation of Fatty Acid Synthase by STAT5A Diabetes, July 1, 2005; 54(7): 1968 - 1975. [Abstract] [Full Text] [PDF]

				I K Lund, J A Hansen, H S Andersen, N P H Moller, and N Billestrup Mechanism of protein tyrosine phosphatase 1B-mediated inhibition of leptin signalling J. Mol. Endocrinol., April 1, 2005; 34(2): 339 - 351. [Abstract] [Full Text] [PDF]

				R. Garzon, S. F. Soriano, J. M. Rodriguez-Frade, L. Gomez, A. Martin de Ana, M. Sanchez-Gomez, C. Martinez-A, and M. Mellado CXCR4-mediated Suppressor of Cytokine Signaling Up-regulation Inactivates Growth Hormone Function J. Biol. Chem., October 22, 2004; 279(43): 44460 - 44466. [Abstract] [Full Text] [PDF]

				C. A. Shang and M. J. Waters Constitutively Active Signal Transducer and Activator of Transcription 5 Can Replace the Requirement for Growth Hormone in Adipogenesis of 3T3-F442A Preadipocytes Mol. Endocrinol., December 1, 2003; 17(12): 2494 - 2508. [Abstract] [Full Text] [PDF]