Analysis of growth hormone effects on hepatic gene expression in hypophysectomized rats

Abstract

As indicated by its name, the Growth hormone is the main regulator of longitudinal growth in mammals. GH is mainly produced in the pituitary gland and acts distantly on target tissues through the activation of the transmembrane GH receptor. The liver expresses the highest content of GH receptor. Accordingly, the liver is of key importance for the physiological actions of GH. Global expression analysis of the hepatic GH actions using microarrays clearly indicate that most of the known physiological effects of GH can be explained, at least in part, through its effects on the transcription of specific genes. To this end, GH is known to activate a network of transcription factors in liver that include among others the nuclear receptor such as PPAR alpha, CAR or SHP, buts also SREBP CRBP, and STAT5b. The latest is of particular importance in the regulation of body growth through its regulation of the expression of IGF-I and the ALS of the IGFBP3 binding protein which in turn mediate many of the GH actions in extra hepatic tissues. STA75b and presumably the members of the nuclear receptor family under GH control also influence genes involve in xenobiotic metabolism. GH actions in liver lead to increase lipogenesis and decreased aminoacid catabolism, thereby promoting anabolic growth in bone and muscle tissue. These effects can be explained by increase expression of lipogeneic genes as consequence of the activation of the key lipogenic transcription factor SREBP1 as well as diminished expression of PPAR alpha, a transcription factor regulating genes involved in lipid oxidation. In addition, reduced aminoacid catabolism correlates to diminished expression of aminotransferases in liver upon GH treatment. Microarray-based expression profiling of GH actions has not only provided molecular correlates to its known physiological action buts has identified a large number of regulated genes for which physiological function is unknown or poorly understood. This opens the opportunity to increase our understanding of liver physiology and the characterization of novel GH effects.