Transcription Factors in Growth Hormone Action

Regents Of The University Of Michigan - Ann Arbor, Ann Arbor MI

Investigators

Abstract

To understand the basics of normal growth, it is useful to study how growth hormone (GH), a key regulator of normal growth, alters gene function. Studying regulation of the cancer-related gene c-fos by GH, multiple DNA sequences and gene-directing proteins (transcription factors) have been identified that participate in GH action. Most recently, it has been found that the transcription factor known as CCAAT/Enhancer Binding Protein (C/EBP) b plays a wide role in GH-regulated gene expression, and mediates function of multiple genes involved in the physiological actions of GH. This awardee will examine the effects of GH on cells from mice deficient in C/EBP-b (knockouts). The ability of GH to regulate c-fos will be examined first to determine whether the well-characterized regulation of this gene by GH is deficient in the absence of C/EBP-b and can be restored when C/EBP-b is restored in the cells. Then other GH-dependent genes will also be examined in the C/EBP-b cells to determine whether C/EBP-b has a general role in GH-regulated gene expression. The effects of GH on growth will be examined in the C/EBP-b deficient mice. The role of a mediator of GH-stimulated growth, insulin like growth factor 1 (IGF 1), will be tested by crossing the C/EBP-b deficient mice with mice genetically altered in IGF 1 regulation. These studies may identify whether there are common mechanisms involving C/EBP-b by which the actions of GH are coordinated, through changes in GH-regulated programs of gene expression.