Growth disorders are a major concern for patients, their parents, and health care professionals. our understanding of growth failure in the presence of normal GH secretion remains primitive,... Show moreGrowth disorders are a major concern for patients, their parents, and health care professionals. our understanding of growth failure in the presence of normal GH secretion remains primitive, hampering the development of new treatment strategies for children with short stature. Final height gain in currently available therapeutic regimens is restricted by rapid progression of pubertal development and the associated acceleration of growth plate fusion. Both an intact GH-Insulin-like growth factor I (IGF-I) system and estrogen signaling are of pivotal importance for normal growth. Regulation of normal growth is presumably based on the coordinated interplay between these systems, but the underlying molecular mechanisms are poorly understood. The aims of the work described in this thesis were: (1) to increase the understanding of the roles of GH, IGF-I and estrogen in growth plate biology, using a model system of fetal human mesenchymal stem cells (fhMSC) that are able to differentiate along the chondrogenic lineage in a similar fashion as occurs in the growth plate during growth; (2) to explore potential growth-promoting treatment strategies for children with idiopathic short stature (ISS) as an alternative for currently used growth hormone treatment regimens. Show less
