During this reporting period the Laboratory of Genetics and Physiology has made progress in the understanding of mechanisms used by cytokines to control the physiology of liver and muscle. We have established that cytokine signaling (possibly growth hormone) through the transcription factor Stat5 is essential to protect the liver from hepatosteatosis (fatty liver) and its ability to regenerate. In collaboration with other researchers it was discovered that growth hormone and glucocorticoid steroids share common signaling pathways. Notably, the glucocorticoid receptor and the transcription factor Stat5 interact with each other and both components are required for the liver cell to fully respond to either growth hormone or glucocorticoids. This finding provided for the first time a snapshot in how these two signaling pathways are intertwined in hepatocytes. Lastly, we established for the first time that growth hormone signaling in muscle tissue is essential for body growth. Deletion of the transcription factor Stat5, which is a downstream mediator of growth hormone, specifically in muscle cells resulted in mice with reduced body growth during puberty. This physiological consequence was not the result of lower levels of systemic insulin like growth factor I, but rather due to defects in paracrine signaling, possibly between muscle cells and bone.
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