EVOLVING CONCEPTS OF GH AND IGF-I REGULATION OF SKELETAL GROWTH

Unlike the secretion of classic endocrine glands, IGF-I secretion is not restricted to a discrete endocrine gland. IGE-I is secreted by the liver and transported to target tissues where it can act as an endocrine factor. Impor tantly ICF-I is also synthesized by most mesenchymal tissues and in some neuroendocrine and neural sites where IGF-I acts as a local autocrine/paracrine factor regulated by other hormones and local factors in addition to GH. The relative importance of these two modes of IGF-I action varies from tissue to tissue. Cartilage in general and epiphyseal growth plates in particular produce insufficient IGF-I to sustain full normal growth. The evidence reviewed here suggests that IGF-I as an endocrine factor is of major importance in normal growth. In other tissues where IGF-I synthesis is greater, as in the kidney, or sequestered by anatomical barriers, such as in the ovarian follicle, the autocrine/paracrine mode of IGF-I may predominate. In cardiac and skeletal muscle ICF-I acting as an endocrine factor may predominate in GH responses but the autocrine/paracrine mode may be involved in work hypertrophy and regeneration. Both the endocrine and autocrine/paracrine actions of IGF-I are subject to negative and positive modulation by interstitial and plasmatic IGF binding proteins. This aspect of IGF-I action, not considered in this short review, is under very active investigation.