The Pediatric and Reproductive Endocrinology Branch (PREB) focuses on the physiology and pathophysiology of growth, development, metabolic, immune, and reproductive functions and the major neurohormonal systems, the hypothalamic-pituitary-adrenal and -gonadal axes and autonomic nervous system, that subserve these functions. The researchers study both the developmental and static functions of these systems and their key effector molecules, including corticotropin-releasing hormone, arginine-vasopressin, corticotropin, glucocorticoids, gonadotropins, estrogens, progestins, androgens, and the catecholamines, in the in vivo integrated and at the reduced cellular, subcellular, and genomic levels. The branch oversees operation of the NICHD Component of the Inter-Institute Endocrinology, Metabolism and Diabetes Program, directed by Lynnette Nieman, and the Reproductive Endocrinology and Infertility Training Program, which have earned the approval, respectively, of the Accreditation Council for Graduate Medical Education (ACGME) and the American Board of Obstetrics and Gynecology. The branch also participates in the ACGME-accredited Pediatric Inter-Institute Endocrinology and Metabolism Program.

Led by George Chrousos, the Section on Pediatric Endocrinology demonstrated novel mechanisms leading to sporadic, familial, inflammation-related and physiologic glucocorticoid resistance and described a novel molecular mechanism of glucocorticoid resistance in response to inflammatory cytokines and of HIV-1-induced glucocorticoid hypersensitivity, potentially a major pathogenetic factor in the development of AIDS. The researchers also demonstrated that glucocorticoids influence approximately one-fifth of the human genome, including a wide array of genes of the immune response, and described a mechanism whereby glucocorticoids and catecholamines cause the shift from cellular to humoral immunity. Other findings include epinephrine deficiency and insulin resistance, along with inability to elevate glucose levels in response to exercise in children with congenital adrenal hyperplasia. The group demonstrated major changes of HPA axis and immune system functions in normal individuals exposed to acute or chronic sleep loss, in patients with idiopathic chronic insomnia, and in patients with sleep apnea, showing that sleep apnea affects many patients with polycystic ovary syndrome and is part of the metabolic syndrome X.

Under Lynette Nieman, the Section on Reproductive Medicine, together with Dr. Pamela Stratton, head of the Ob/Gyn consultation service, demonstrated that endometriosis had marked comorbidity with the autoimmune disorders fibromyalgia and chronic fatigue syndrome as well as with infertility. The researchers also showed that MRI had poor predictive ability for surgery-proven endometriosis.

Led by Karel Pacak, the Unit on Clinical Neuroendocrinology is investigating the etiology, pathophysiology, diagnosis, prognosis, and treatment of pheochromocytoma and other neuroendocrine tumors. The group introduced plasma-free metanephrine in the diagnosis of pheochromocytoma and PET scanning in the localization of pheochromocytoma tumors, described major differences between such tumors when associated with different multiple neoplasia syndromes, and established molecular markers of benign and malignant pheochromocytoma.

The Unit on Reproductive Endocrinology and Infertility investigated a variety of clinical reproductive disorders. The studies were an integral facet of the Reproductive Endocrinology and Infertility Training Program, directed by James Segars. The research team identified a number of genes specifically associated with fibroids; those genes are now undergoing analysis for clues in uterine muscle tumorigenesis. The team also explored the relation of the Brx protooncoprotein, which it cloned, to estrogen-mediated responses, implicating p38 mitogen–activated protein kinases in estrogen action.