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DEVELOPMENTAL ENDOCRINOLOGY BRANCH
Carolyn Bondy, Chief
The Developmental Endocrinology Branch (DEB) investigates fundamental issues in human growth and development. Physician-scientists in the branch combine clinical and basic research to elucidate genetic, biochemical, and physiological mechanisms underlying normal and disordered developmental processes. For many years, the DEB has been an international leader in the diagnosis and treatment of short stature. The branch continues at the forefront of this field with recent studies by Jeffrey Baron and Carolyn Bondy illuminating fundamental cell biological and molecular mechanisms of epiphysial growth plate elongation. In addition, Dr. Baron’s group has made important contributions to the diagnosis of pediatric osteoporosis by showing that current DEXA densitometry significantly underestimates bone mineralization in children. As has become abundantly clear in recent years, the development of obesity in children is one of the most important and challenging medical problems of our time. Jack Yanovski’s pioneering work has brought the DEB to a leadership role in this important new field. His investigations into genetic and epigenetic interactions in the development of obesity are coupled with clinical trials of new treatment modalities for pediatric obesity. The DEB has a long-standing interest in ovarian function and has made many important contributions in this arena of women’s health. Lawrence Nelson is a leader in the study of premature ovarian failure among the world’s largest group of such patients. In recent years, his laboratory has made important advances on both the clinical and basic fronts, showing, for example, that autoimmunity is responsible for less than 5 percent of cases of premature ovarian failure. In addition, the laboratory has identified a novel, oocyte-specific maternal effect gene, termed Mater, that is required for activation of the zygotic genome and embryonic development beyond the two-cell stage. Dr. Bondy also conducts research in women’s health, focusing on Turner syndrome to elucidate the role of X-chromosome genes in growth, brain, and ovary development and metabolic functions. In addition, her laboratory has made important, novel discoveries about the normal role of androgen in women, demonstrating that testosterone protects the mammary epithelium from estrogen-induced proliferation. The group has also shown that estrogen treatment promotes IGF1 expression in the primate prefrontal cortex and that IGF1 augments neuronal glucose utilization, process growth, and synapse formation, suggesting potential mechanisms for estrogen’s neuroprotective effects. Since hyperactivity of the hypothalamic pituitary adrenal (HPA) has been implicated in the pathogenesis of a number of psychiatric and metabolic disorders, Greti Aguilera’s research has been elucidating the mechanisms underlying modulation of the stress response. The DEB studies the regulation of hypothalamic peptides corticotropin releasing hormone and vasopressin and their pituitary receptors under different stress situations as well as the consequences of such regulation on adrenal steroidogenesis. Constantine Stratakis’s research focuses on adrenal organogenesis and tumor formation. His pioneering combination of genetic and endocrine analytic strategies has powered major discoveries into mechanisms in endocrine tumor formation as well as clinical diagnoses of complex and rare endocrine syndromes. His laboratory has already attained international recognition and is one of the most productive groups in the institute.