STAT5 signaling in sexually dimorphic gene expression and growth patterns

The past 10 years have seen enormous advances in our understanding of how c ytokine signals are mediated intracellularly. Of particular significance wa s the discovery of a family of seven Signal Transducer and Activators of Tr anscription (STAT) proteins, Each of these has now been studied in detail, and appropriate gene-disrupted mouse models are available for all except ST AT2 (Leonard and O'Shea 1998). Fetal lethality is observed in Stat3-deficie nt mice, and various immunodeficiencies characterize mice with disrupted St at1, Stat4, and Stat6 genes, which is consistent with impaired signaling fr om the specific cytokines that activate each of these proteins. The recent characterization of Stat5-deficient mice has led to several unanticipated f indings that point to diverse biological functions for the two STAT5 forms, STAT5a and STAT5b. These include roles for one or both STAT5 forms in the immune system, hematopoiesis, sexually dimorphic growth, mammary developmen t, hair growth, deposition of adipose tissue, and pregnancy.. Here we revie w the hormone- and cytokine-activated signaling pathways in which STAT5 par ticipates and the extensive evidence, from laboratory animals, that these f actors are required for sex-specific aspects of development, including cont rol of body size. Finally, we consider human growth disorders that may invo lve defects in STAT5-dependent signal transduction.