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HYPOPHYSECTOMIZED rats have a defect in the synthesis of matrix protein which is rapidly repaired by the administration of GH in vivo. In 1957, it was first reported that this defect, as determined by measuring the incorporation of 35Ssulfate into chondroitin sulfate, could not be corrected by addition of GH to media containing cartilage segments (1). The defect, however, was rapidly corrected by the addition of diluted normal rat serum to such media, but serum from hypophysectomized rats was virtually inactive. It was proposed that GH acted on skeletal tissues by inducing the formation of a direct acting intermediary growth factor. This hypothesis, commonly referred to as the somatomedin hypothesis, has been extensively confirmed and recently extended to include autocrine and paracrine roles of somatomedins in many tissues as well as the originally recognized endocrine role of this growth factor. Research in the somatomedins has increased so much in recent years that a comprehensive review of the subject is no longer possible within the length constraints of this Journal. In this review, we will focus on the insulin-like growth factors (IGFs) that are present in body fluids and tissues. We will review the rapidly developing information about the molecular biology of the biosynthesis of IGFs and their regulation in fetal and postnatal life and the possible role of IGF biosynthesis in tissue repair and hypertrophy. Last, we will consider the relative contribution of endocrine as opposed to autocrine/paracrine actions of IGF-I in skeletal growth. Not included in this review will be a consideration of IGF binding proteins, IGF receptors, and postbinding effector mechanisms. Readers are referred to recent reviews for consideration of these topics (2–4).
Daughaday et al. (Wed,) studied this question.