Mode of Action of Pituitary Growth Hormone on Target Cells

Although the results of growth hormone (GH) action on somatic growth are easily recognized, the site and the cellular mechanism(s) behind these effects of the hormone are unclear. One of the major obstacles in the exploration of the mechanisms of action of GH at the cellular level has been the lack of concor­ dance between in vivo and in vitro effects. Administration of GH in vivo to GH-deficient animals or man results in a marked stimulation of chondrogenesis and myogenesis, resulting in accelerated somatic growth (for reviews see 1 1, 16, 59, 6 1, 88), However, when added in vitro to explants of cartilage or incubated muscle preparations, GH exerts small and inconsistant effects on growth-associated parameters (59). This discrepancy between the in vivo and in vitro effects of GH plus the identification and subsequent chemical charac­ terization of GH-dependent plasma peptides-in this review called soma­ tomedin(s) or insulin-like growth factors-has led to the concept that GH stimulates cell proliferation indirectly via somatomedins. According to the somatomedin hypothesis, GH has no direct effects on cartilage but instead stimulates chondrogenesis and subsequent growth by increasing the level of somatomedins. These in tum stimulate several growth-associated parameters in cartilage and other tissues. The somatomedins are synthesized and released primarily from the liver in response to GH ( 16, 48). The aim of this review is to discuss the role of direct effects of GH at the cellular and tissue level resulting in the physiological effects attributed to GH action. There will be a special emphasis on recent studies suggesting direct effects of GH on differentiation and proliferation of its target cells.