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Program in Reproductive and Adult Endocrinology
The Program in Reproductive and Adult Endocrinology (PRAE) can point to a broad, comprehensive, and exceptional list of publications and activities in the areas of endometriosis, fibroids, infertility, and endocrine aspects of disease—both basic and clinical. The Program has earned recognition as a national leader in the field; in fact, 10 percent of the papers accepted for presentation at a recent annual meeting of the American Society for Reproductive Medicine came from the PRAE.
The Section on Implantation and Oocyte Physiology, led by Alan DeCherney, has been working on the regulation of blasotcyst development using the in-vitro fertilization (IVF) approach with both mouse and primate animal models. Investigation is being carried out on the pre- and peri-implanation embryos’ signaling pathways that regulate oxygen, growth factors, and extracellular matrix. Work also continues on a non-invasive method to obtain fetal cells that migrate into the cervical canal during the first trimester, which facilitates the differentiation among a blighted embryo, normal pregnancy, and ectopic pregnancy. This single-cell investigation will permit earlier and more sophisticated prenatal diagnosis.
The Section on Reproductive Medicine, headed by Lynnette Nieman, works on the hypothalamic pituitary adrenal axis in pregnancy, which presents a challenge for detecting disease and assessing the relative merits of immunometric and radioimmunoassay measurement of ACTH for differential diagnosis of Cushing’s syndrome. The Section continues its work on the diagnosis and management of patients with hypercortisolism, recently focusing on ectopic ACTH-secreting tumors and their localization. Another focus of the Section’s work is endometrial physiology and endometriosis pathologies. It has published studies on the endometrium, describing the localization of lesions in women with endometriosis and characterizing the estrogen alpha receptor and use of raloxifene as an adjunct treatment for endometriosis. The Section found that staining of CD10, a cell-surface metalloendopeptidase present in normal endometrium, is helpful in diagnosing endometriosis.
The Section on Medical Neuroendocrinology, under the direction of Karel Pacak, continues to focus on neuroendocrine disorders, particularly pheochromocytoma. The Section used micro-computed tomography for early diagnosis of ectopic pheochromocytoma tumor in the liver of the nude mouse, a technique that may be applied to the human model and that would be an excellent way to diagnose early small metastases. In addition, members of the Section noted that mutations of the SDHB gene are associated with one-half of all malignancies originating from extra-adrenal paragangliomas. The high frequency of SDHB germline mutations among patients with malignant disease, particularly when originating from adrenal paraganglioma, may justify a high priority for SDHB germline-mutation testing in such patients.
The Section on Clinical Genomics, led by Owen Rennert, applies information gained from biochemical and genomic studies to clinical investigations. Members of the Section on Clinical Genomics cloned several genes, including the novel mArd2, which demonstrates testis specificity and elevated expression in pachytene spermatocytes. Subsequent studies showed that Ard2 has acetyltransferase activity and may be responsible for compensating for the loss of X-linked transacetylation activity during meiosis and post-meiotic differentiation in germ cells. The Section also applied genomic approaches to the study of human diseases, designing two hybridization-based high-throughput methods for screening risk factors for thrombophilia and age-related macular degeneration. The methods will provide a more accurate tool for risk calculation and disease prediction for these two complex disorders.
James Segars and the Unit on Reproductive Endocrinology and Infertility addressed disparities in access to reproductive services and treatment. Collaborative work established a complex relationship between the BRX gene complex and fibroid generation, and the Unit is expanding its work on several aspects of fibroids, including gene regulation and growth factors. With regard to fertility, the Walter Reed Army Medical Center’s Assisted Reproductive Technologies Program continues to provide material for clinical studies. The Oocyte Physician Program, involving investigators at the NIH and the laboratory of Jacques Cohen in Livingston, New Jersey, looked at the effect of leiomyomas on early pregnancy, anti-Müllerin hormone pre- and post-myomectomy, and ovarian reserves in patients with fibroids. A new area of investigation has been the assessment and preservation of ovarian function in women and girls undergoing cancer treatment.