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Program in Reproductive and Adult Endocrinology

Director: Alan DeCherney, MD

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The Program in Reproductive and Adult Endocrinology (PRAE) conducts biomedical research and training as well as clinical activities in the area of reproductive endocrinology and adult endocrinology. Physician-scientists from all Sections and Units of the Program admit patients to NIH's Clinical Research Center for research-directed, approved clinical protocols and see patients in the outpatient setting for protocol evaluation, follow-up, and consultations. The PRAE trains fellows in Adult Endocrinology well as Reproductive Endocrinology and Infertility (REI), the former being approved by the Accreditation Council for Graduate Medical Education (ACGME) and the latter by the American Board of Obstetrics and Gynecology. The Program takes three REI fellows (one of whom is in the military track) and two medical endocrine fellows per year. The medical endocrinology training program (The NIH Inter-Institute Endocrinology Fellowship Program) is a joint effort with the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the National Institute of Dental and Craniofacial Research (NIDCR). The PRAE collaborates closely with the Pediatric Endocrine Fellows, and all three fellowships include rotations on the adult endocrine unit and joint conferences. Elective time has been added to allow the fellows the opportunity to obtain advanced degrees (e.g., an MPH, Duke University Program in Clinical Research).

Lynnette Nieman leads the Section on Reproductive Endocrinology, which currently conducts a clinical and basic research program on cortisol physiology and pathophysiology. Previous studies with the antiprogestin CDB-2914 formed the basis for FDA approval of the agent as a morning-after pill in 2010; it was submitted to the EMEA (European Medicines Agency) in 2012 for approval for the treatment of symptomatic leiomyoma. Nieman’s research interest in both adrenal and reproductive steroids dates to her initial work, in 1983, with the antiprogestin and antiglucocorticoid agent mifepristone. Since that time, her group has helped to develop diagnostic tests and their interpretation for the differential diagnosis of Cushing’s syndrome, including salivary and midnight cortisol, 8 mg dexamethasone suppression, the CRH stimulation test, the dexamethasone-CRH test, inferior petrosal sinus sampling, and high dose Octreoscan and FDG-PET imaging. The work continues with current studies on F-DOPA PET and the use of mifepristone for the treatment of ectopic ACTH secretion. A database of Cushing’s syndrome patients has been constructed. Current studies explore aspects of glucocorticoid action and will continue. Nieman’s research has shifted away from fibroid study. It is planned that this Section will change its name to Section on Clinical and Translational Endocrinology to more accurately reflect current research emphasis.

The Section on Medical Neuroendocrinology, led by Karel Pacak, was established in 2001 to develop novel approaches for the diagnosis, localization, and treatment of pheochromocytoma (PHEO) and to search for new molecular and genetic markers to the etiology of this tumor. Initial studies focused on the development of novel methods and criteria to diagnose and localize pheochromocytoma. Current studies focus mainly on how to further characterize the tumors, using functional imaging approaches, identifying new molecular and genetic mechanisms of tumorigenesis, and introducing new treatment options for malignant pheochromocytoma. Currently, the Section has the world's largest population of patients with malignant and succinate dehydrogenase subunit B–related pheochromocytomas. The Section also established a unique PHEO tumor tissue and blood bank to assist in its research and objectives. The Section also promotes interactive dialogue between patients and healthcare professionals by introducing and organizing a series of conferences in collaboration with the Pheochromocytoma Research Support Organization (PRESSOR). The Section’s current goal is to introduce new algorithms for diagnosis and localization of PHEO) in order to: (i) explain the molecular basis for different clinical presentations and establish the pathways of tumorigenesis (focusing on genotype-phenotype correlations in various pheochromocytomas, using gene expression and proteomic profiling); (ii) search for new molecular and genetic markers for diagnosis and treatment of malignant pheochromocytoma (using microarray and proteomic approaches and evaluating new chemotherapeutic compounds that target identified proteins and pathways); (iii) facilitate new and improved collaborations and inter-disciplinary studies and support a coordinated approach to basic and clinical research, which should lead to an improved understanding of the biology of pheochromocytoma and more rapid advances in treatment for patients with malignant tumors.

The Unit on Reproductive Endocrinology and Infertility is led by James Segars. A major focus of the Unit is the importance of molecules that interact with the gonadal steroid receptors in development of reproductive tissues (uterus, ovary, breast) or tumorigenesis. A second focus is the pathobiology of common and rare uterine leiomyomata (fibroids) and the underlying abnormalities in signal transduction, particularly relating to the estrogen receptor–interacting, A-kinase anchor protein AKAP13 and to extracellular matrix formation. In addition to its basic and translational studies, the Unit has forged collaborations with NCI and NHGRI to study rare fibroid syndromes using SNP arrays, followed by the next-generation sequencing technique of whole-exome sequencing, as an approach to develop an understanding of the genetic underpinnings in rare cases of hereditary, early onset fibroids. Segars also initiated and, with Paul Driggers, co-directs the NICHD-sponsored leiomyoma tissue bank.

Segars also serves as the director of the Reproductive Endocrinology and Infertility Training Program and supervises Reproductive Endocrine Fellows on various clinical projects related to infertility, assisted reproduction, and clinical outcomes.

The Unit on Reproductive Regenerative Medicine is led by Erin Foran Wolff. Wolff is a 2010 PRAE REI Fellowship graduate and was selected by a formally constituted NICHD Assistant Clinical Investigator Search Committee in a competitive process. For her independent translational research, Wolff is working with National Institute of Heart, Lung and Blood (NHLBI) under John Tisdale and with NICHD under Alan DeCherney. The scope of her work includes characterization of the effects of stem cell therapies on the reproductive tract, with the long-term goal of developing cellular therapy applications for gynecologic conditions.

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