Plasma somatomedin : studies on some of its characteristics and on its relationship with growth hormone

Growth is the most characteristic feature of childhood. It also represents the best index of a child's well-being since so many prerequisites must be fullfilled for its harmonious course and such a multitude of pathological factors can interfere with it. It is not surprizing that careful monitoring of growth is common practice for all who are responsible for the health of children. Registering abnormality of a growth pattern is relatively easy. Discovering the cause of the disturbance amongst the vast array of possibilities however, is frequently very difficult. Amongst the major prerequisites for normal growth we should first mention the intactness of the dividing capacity of all cells and the integrity of specific functions such as e.g. collagen production by the chondrocytes. Equally important is the supply of nutrients: the availability of enough food of good quality, normal absorption, adequate transformation into elementary molecules, and normal transport into the cells. Disturbances in these functions, which can best be characterized as potentially rate limiting, represent the most frequent causes of stunted growth. The role of hormones is quite different since they are rate setting, and thus exert the overall control of growth. Their own secretion is regulated in most instances by the central nervous system, which-integrates stimuli of a wide variety: 'substrate' signals (such as glucose with respect to GH-secretion), hormone signals (e.g. feedback-regulation), integrated stimuli from within the body (e.g. sleep) and from the outside world ranging from simple visual impressions to complex ones such as emotional deprivation. Certain nuclei of the hypothalamus translate these integrated impulses into the synthesis and secretion of specific releasing hormones which reach the anterior pituitary gland through the portal system and stimulate the secretion of selected pituitary hormones. All anterior pituitary hormones are involved in the regulation of growth rate. The most important amongst them is growth hormone (GH). It has long been thought that GH exerted a direct action on the growth rate of tissues. The discovery of sulfation factor (SF), later termed somatomedin (SM), and Daughaday's hypothesis on its role as the mediator of GH's growth promoting effect, places GH in line with the other anterior pituitary hormones which all have their major effect through secondary hormones. If this hypothesis proves to be correct, SM would represent the major regulator of growth rate. In this thesis our own work on SM is reported and related to the progress made by others. The investigations of Daughaday and of Salmon leading to the discovery of somatomedin and of its potential importance for human pathology are summarized in chapter one. The results of our own and collaborative work make up chapter two. Initially we have addressed ourselves to the characteristics of somatomedin in human plasma (section A). Intrigued by the question which organ or organs are producing SM, the early localization of growth hormone in the rat was studied (section B)

Hyperthyroxinaemia due to decreased peripheral triiodothyronine production

Two patients, a boy of 8 and a woman of 60 years of age, had higher than normal levels of serum total thyroxine (T4), free T4 (FT4), FT4 index, and reverse triiodothyronine, but normal serum triiodothyronine (T3) levels. The pituitary-thyroid axis could be normally stimulated by thyrotropin-releasing hormone, suggesting euthyroidism at the pituitary level. High levels of serum T4-binding globulin decreased during T3 treatment in the boy. Studies show that in these patients a raised serum FT4 is necessary to produce in the peripheral tissues sufficient amounts of T3 for biological action. Two possible mechanisms for a basic defect underlying this newly recognised syndrome are proposed: inhibition of T4 transport into tissue cells and reduced intracellular 5'-deiodinase activity catalysing T4 to T3 conversion