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20## Annual Report of the Division of Intramural Research, NICHD National Institutes of Health Eunice Kennedy Shriver National Institute of Child Health and Human Development

Alan DeCherney, MD, Chief

The Reproductive Biology and Medicine Branch (RBMB) can point to a broad, comprehensive, and exceptional list of publications and activities in the areas of endometriosis, endocrine aspects of disease both basic and clinical, fibroids, and infertility. The Branch is recognized as a national leader in the field; in fact, 10 percent of the papers accepted for presentation at the American Society for Reproductive Medicine Annual Meeting came from RBMB. No other institution in the country has anywhere near that record.

The Section on Medical Neuroendocrinology, under the direction of Karel Pacak, has made significant contributions in the neuroendocrine area, particularly pheochromocytoma. A primary emphasis during 2006 was the use of micro CT for early diagnosis of ectopic pheochromocytoma tumor in the liver of the nude mouse, a technique that can be applied to the human model and would be an excellent way to diagnose early small metastases. In addition, members of the group 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 germ-line mutations among patients with malignant disease, particularly when originating from adrenal paraganglioma, may justify a high priority for SDHB germ-line mutation testing in such patients.

The Section on Reproductive Medicine, headed by Lynnette Nieman, published a landmark article in Endocrine Reviews on the hypothalamic pituitary adrenal axis in pregnancy, which presents a challenge for disease detection. In addition, the Section published a clinical paper comparing immunometric and radioimmunoassay measurement of ACTH for differential diagnosis of Cushing's syndrome. Given the inaccuracy of earlier diagnostic tests for and the importance of diagnosing Cushing's syndrome, the paper is an important contribution. The laboratory continues its excellent work in the diagnosis and management of patients with hypercortisolism, recently focusing on the diagnosis and management of ectopic ACTH-secreting tumors and their localization. The Section continues to focus on 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 adjunctive treatment for endometriosis. CD10 cell-surface metalloendopeptidase is present in normal endometrium, and staining of this protein is helpful in diagnosing endometriosis.

James Segars heads the Unit on Reproductive Endocrinology and Infertility, a reproductive endocrine group that continues to be extremely productive and innovative. During 2006, the laboratory 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 laboratory is expanding its work on several aspects of fibroids, including gene regulation and growth factors. The primary hypothesis posits that fibroid growth is in some way associated with attempts at healing and inflammation.

With regard to fertility, the Walter Reed Army Medical Center's Assisted Reproductive Technologies program continues to provide excellent material for clinical studies. In addition to continuing to capitalize on and encourage work already in progress, the Center plans to enlarge its consultative service; to increase the number of fellowships to three per year (already approved), thus making Walter Reed's fellowship program the largest Reproductive Endocrinology and Infertility Fellowship Progam in the country; and to develop several protocols, including one on the mechanisms and treatment of abnormal bleeding. A major effort will focus on treating patients diagnosed with cancer who wish to preserve fertility through the use of various drug regimens. In addition, the oocyte physician program is almost entirely in place, involving investigators at the NIH and the laboratory of Dr. Jacques Cohen in Leviathan, New Jersey; recruitment for an implantation scientist is moving along well.

The Branch will be further strengthened with the planned addition of Larry Nelson, whose interests lie in premature ovarian failure, and the collaboration of others in the Institute. The RBMB's ability to evaluate clinical entities, including those of neuroendocrine and adrenocortical systems, and apply these insights to diagnosis and treatment is apparent.

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