Mechanism of the Stimulatory Effect of Growth Hormone on Longitudinal Bone Growth*

AT THE beginning of this century Aschner (1) demonstrated a relationship between a factor in the pituitary and body growth. In subsequent experiments Evans and Long (2) produced supranormal growth in intact rats with administration of bovine pituitary extracts. In the 1940s a highly purified protein was isolated from bovine pituitaries (3, 4) that produced somatic growth when administered to hypophysectomized or normal rats. This protein exhibited no or small effects on the gonads and the thyroid gland and was called GH or somatotropin. The molecular structure of GH was not revealed until the beginning of the 1970s when the total amino acid sequence of GH was determined (5, 6). As early as 1923 Dott and Fraser (7) observed a decrease in epiphyseal cartilage width in cats and dogs after hypophysectomy. Dott (8) also found that treatment with extracts from the anterior pituitary lobe partially reversed this effect. Freud and co-workers (9) found that GH increased the nose-tail length in hypophysectomized rats by increasing the thickness of growth zones in the tail vertebrae, suggesting that GH increases the thickness of the growth plate by stimulating the proliferation of chondrocytes.