Molecular mechanism of growth hormone signalling.

GH exerts a wide variety of biological actions in many different tissues and cell types. The actions of GH at the cellular level can be divided into three categories: metabolic, mitogenic and differentiation. Metabolic effects of GH have been well documented and characterized in adipocytes. The major effect of GH in adipocytes from intact animals is an anti insulin-like or diabetogenic effect [1], where GH treatment leads to decreased glucose utilization and lipogenesis and increased lipolysis [2]. In contrast, in adipocytes from hypophysectomized animals GH exhibits insulin-like effects including increased glucose uptake and stimulation of lipogenesis [3]. The metabolic effects of GH have been described in skeletal muscle, heart and kidney where both glucose and amino acid uptake are stimulated by GH [4] as well as an increase in general protein biosynthesis. Proliferative effects of GH have been described in liver, kidney and heart after in vivo administration of GH [5]. Evidence for a direct effect on cell proliferation has been provided by in vitro experiments in which it has been described that GH can stimulate the mitotic activity of many different cell types [6-8]. In pancreatic f3-cells GH was found to increase the mitotic activity 10-fold by an insulin-like growth factor 1 (IGF-1) independent mechanism [9]. Direct effects of GH on cell proliferation have also been described in cultured chondrocytes [6], smooth muscle cells [10] and thymocytes [11]. Differentiation of