THE ENDOCRINE SOCIETY 2003 ANNUAL AWARDS


    Citation for the 2003 Fred Conrad Koch Award of The Endocrine Society to Dr. Maria Iandolo NewGo
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Dr. Maria New has accumulated a body of work that marks her as one of the premier clinical scientists of our time. Dr. New’s seminal contributions to steroid endocrinology include her discovery of apparent mineralocorticoid excess (AME), a disease with severe low-renin hypertension, hypoaldosteronism, and low secretion of all adrenal steroids, resulting from a pathogenetic mechanism. This work opened a new field of receptor biology in humans. In AME, the deficiency of 11ß-hydroxysteroid dehydrogenase (11ß-HSD2) prevents metabolism of cortisol to cortisone and the mineralocorticoid receptor of the distal renal tubule becomes overwhelmed by cortisol. Thus, the overactivation of the receptor by excess ligand is key to the pathogenesis of hypertension. Her team was first to publish mutations on the 11ß-HSD2 gene. She also discovered a second form of low-renin hypertension known as dexamethasone-suppressible hyperaldosteronism.



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FIG. 1.
 
Dr. New is recognized as a world authority on congenital adrenal hyperplasia (CAH). Her achievements include: 1) establishing aldosterone deficiency as a cause of salt wasting; 2) delineating hormonal norms for classical and nonclassical CAH; 3) demonstrating mutations of CYP21 causing 21-hydroxylase deficiency; and 4) pioneering prenatal diagnosis and treatment based on molecular genetic analysis, which has been shown to be safe for both mother and child. She has one of the largest CAH patient populations in the world, carefully documented with clinical, hormonal, and molecular genetics data over some 40 yr. She has conducted prenatal diagnosis of over 600 pregnancies. Her protocol for classically affected females diagnosed and treated before 9 wk produces either normal or significantly less virilized genitalia. This is the only genetic disorder effectively treated prenatally, avoiding wrong sex assignment, mutilating surgery, and psychological damage to both the child and family.

Ongoing work includes genotype-phenotype correlation and a study of gender identity in adult women with CAH. She has also initiated work on a mouse model of CAH to develop gene therapy. Finally, in 1999, she reported the first cases (in two sisters) of partial resistance to all steroids (glucocorticoids, mineralocorticoids, and androgens) but not to thyroid hormones or to vitamin D, suggesting the first global transcription factor defect in humans. Maria New’s work has impacted the world of Pediatric Endocrinology in a way rarely achieved in the past century. She is an ideal candidate for the 2003 Koch Award.

Bert W. O’Malley


    Citation for the 2003 Ernst Oppenheimer Award of The Endocrine Society to Dr. Donald P. McDonnellGo
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Donald P. McDonnell, the recipient of the 2003 Ernst Oppenheimer Award, is the Glaxo-Wellcome Professor of Pharmacology and Molecular Cancer Biology at Duke University Medical Center. Donald obtained a B.S. degree in Biochemistry from the National University of Ireland in Galway in 1983 and subsequently a Ph.D. in Cell Biology from Baylor College of Medicine in Houston under the mentorship of Dr. Bert O’Malley. His doctoral work culminated in the cloning of the vitamin D receptor and the demonstration that it is a member of the nuclear receptor superfamily. To further pursue his interest in the molecular pharmacology of steroid hormone receptors, Donald took a postdoctoral fellowship at SmithKline Pharmaceuticals, where he developed a yeast model system in which he could effectively reconstitute steroid hormone-dependent transcription. Notably, he and his colleagues used the power of yeast genetics to show that corepressors were an integral part of nuclear receptor signal transduction. Donald returned to the Department of Cell Biology at Baylor as a faculty member in 1990, where he documented that agonist and antagonist ligands induced specific conformational states in nuclear receptors.



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FIG. 2.
 
Donald was induced to leave academia for industry a second time to pursue his interest in exploiting the molecular complexity of steroid hormone signal transduction pathways for the development of novel hormone therapeutic agents. At Ligand Pharmaceuticals, he established a discovery group that was able to capitalize on these advances and bring to the clinic several new selective estrogen receptor modulators (SERMs), compounds of great biomedical importance for the prevention and treatment of breast cancer and in hormone replacement therapy.

In 1994, Donald joined the faculty at Duke University Medical Center, where his continuing research has provided a firm mechanistic foundation for understanding the basis for differences in the relative agonist/antagonist activities of SERMs in different target cells. Using a combination of receptor mutants and a spectrum of cell types and synthetic hormones, Donald provided intriguing evidence that the estrogen receptor can adopt a spectrum of conformations, reflective of the structure of the ligand, thereby engendering distinct agonist vs. antagonist activities. Donald’s work provided direct evidence for unique receptor conformations by applying the powerful technique of phage peptide display libraries to probe the conformations of various hormone-receptor complexes. This work is widely recognized as providing the basis for understanding how ligand-induced changes in receptor conformation can result in differential interaction with coregulators that underlie the intricate, combinatorial control resulting in the distinctive biology of different SERMs.

The McDonnell group spearheaded the development of a new class of nuclear receptor antagonists that function by directly targeting receptor-coregulator interactions. These novel antagonists, derived from their phage display peptide libraries, function on diverse nuclear receptors, including the estrogen, androgen, progesterone, and vitamin D receptors. Major pharmaceutical companies have adopted the general approach highlighted by this work in their search for nuclear receptor modulators.

By introducing an estrogen-regulated reporter transgene construct into the mouse, Donald’s laboratory has recently developed an estrogen receptor indicator (ERIN) system in which the distinctive pharmacology and activities of SERMs, environmental estrogens, hormonal substances in foods, and other synthetic compounds can be rapidly evaluated in numerous tissues in a well-understood experimental animal species. Donald has further continued his interest in modulators of nuclear receptor action by recently identifying a new corepressor, repressor of tamoxifen activity (RTA). His group has also performed fundamental work on characterization of the two progesterone receptors and in documenting that progesterone receptor A and B have very distinct biologies.

Donald’s work on the molecular pharmacology of nuclear receptors has been recognized through several awards, most notably The Endocrine Society’s Weitzman award, the John J. Abel Award from the American Society of Pharmacology and Experimental Therapeutics, and the North American Menopause Society Research Award.

Donald is full of ideas; he thinks critically about future research directions, and he has the knack for focusing on important aspects worthy of study. Donald’s energetic approach to science is matched by his enthusiasm for life, for his family, and for anything Irish. His positive, engaging manner and fun-loving approach are infectious to both colleagues and friends alike. He is equally comfortable being a leader in his field as he is at being the life of the party.

For his broad and innovative approaches that have advanced our understanding of the molecular biology and pharmacology of nuclear receptors in fundamental ways, Donald P. McDonnell is a most worthy recipient of the 2003 Ernst Oppenheimer Award.

Benita S. Katzenellenbogen


    Citation for the 2003 Robert H. Williams Distinguished Leadership Award of The Endocrine Society to Armen H. Tashjian, Jr.Go
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Dr. Armen H. Tashjian, Jr. is an outstanding leader in research, teaching, and service in endocrinology. In manifestations of this leadership, the breadth and depth of his interests and his unmatched enthusiasm make him unique.



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Dr. Tashjian received his undergraduate education in 3 yr at Yale, and then his M.D. from Harvard in 1957, where he was an intern and resident in medicine on the Harvard Service at Boston City Hospital. From 1959–1961, he was a Clinical Research Associate at NIH, and then he returned to Harvard, beginning with a joint appointment as a Research Fellow in Pharmacology in the Medical School and School of Dental Medicine and progressing rapidly through the faculty ranks to Professor of Pharmacology in 1970. In 1978, he also became Professor of Toxicology at the School of Public Health and Director of the Laboratory of Toxicology. An indication of his leadership as an administrator is that the laboratory expanded and thrived, and in 1991 it became the Department of Molecular and Cellular Toxicology with Dr. Tashjian as the founder and first Chair. Under his leadership, this department was a pioneer in demonstrating the importance of understanding the mechanisms of toxicity of environmental chemicals and therapeutic agents.

Armen Tashjian’s major research accomplishments have been focused in two areas. One is the regulation of extracellular Ca2+. He demonstrated that human medullary thyroid carcinomas produced calcitonin, developed the first RIA for calcitonin, used the assay to identify individuals at risk for these carcinomas, and demonstrated that prophylatic thyroidectomy prevents development of the malignancy. He showed the importance of arachidonic acid and prostaglandins in skeletal homeostasis and their physiological and pathological role in the actions of growth factors and cytokines on bone formation and resorption.

His second area of focus is intracellular mechanisms of hormone action. In the late 1960s, Armen Tashjian demonstrated that it was possible to culture multiple differentiated endocrine cell strains and that these strains could produce and respond to hormones. It is difficult now to picture how exciting it was then to realize that it would be possible to investigate hormonal mechanisms in depth in ways not possible in animals or organ culture. Dr. Tashjian focused on GH cell strains, which he showed secreted GH and prolactin. One of his early observations with these cells was the unexpected finding that TRH stimulated release of prolactin in addition to TSH, the first demonstration that there was not a simple relationship of one hypothalamic releasing hormone to one anterior pituitary hormone. Dr. Tashjian performed in-depth analysis of the actions of TRH, beginning with the biochemical characterization of its receptor, and ultimately cloning the receptor and characterizing its regulation. He elucidated the role of Ca2+ in TRH-induced actions and identified the sources of increases in free cytosolic Ca2+ as both intracellular and extracellular.

Dr. Tashjian was elected President of the American Society for Bone and Mineral Research and of the International Conferences on Calcium-Regulating Hormones. He was chairman of the Scientific Program Committee of The Endocrine Society from 1983–1985, during which time the meetings acquired the frenetic pace to which we are now accustomed. He has been on the editorial boards of The Journal of Clinical Endocrinology & Metabolism, Endocrinology, and Endocrine Reviews, as well as many other journals, and he is an Edwin B. Astwood awardee of The Society.

Throughout his career, regardless of administrative responsibilities, Armen Tashjian did the essential thing necessary for good teaching, which is to teach. He taught a graduate course at Harvard, Cellular and Molecular Endocrinology, for over 30 yr; students ranked it among the best.

Armen was mentor to 99 graduate students and postdoctoral fellows, and 44 of these are female. He was one of the very few people that I knew in 1970 who expected that female fellows would obtain exactly the same kinds of jobs that male fellows would, and he treated us accordingly. This kind of support was invaluable, and it’s difficult to realize now how rare it was then. Armen is also a tremendous mentor because he is enthusiastic. Some people talk enthusiastically, but Armen listens enthusiastically. His complete attention results in questions that are thought provoking and stimulating, exactly what is most useful in discussion of experiments. His curiosity and ability to absorb information are part of what has given him an enormous knowledge of science, not just in endocrinology, but in many fields, that makes all scientific conversations with him exciting.

His enthusiasm clearly permeates all aspects of his life, showing when he talks about his wife and daughters, their travels, and their careers. Those of us who had him as a mentor think of his blue sneakers, bow ties, and yellow note pads with affection, and of the enthusiasm that he shared with us about science with profound gratitude.

Priscilla Dannies


    Citation for the 2003 Edwin B. Astwood Award Lecture of The Endocrine Society to Dr. Jeffrey S. FlierGo
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Over the last 25 yr, Jeff Flier has made remarkable contributions to our understanding of the molecular basis for insulin resistance, the biology of leptin, and the pathogenesis of obesity.



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Beginning in 1974, Flier hypothesized that a group of patients with severe insulin resistance might be suffering from an autoimmune disorder. He designed an assay to demonstrate antibodies against the insulin receptor, thus defining this disease and producing a unique tool for the study of the insulin receptor molecule. He identified acanthosis nigricans as common in women with hyperandrogenism with insulin resistance and was first to identify that both insulin and IGF-1 receptors are expressed and functional in human ovary. He then characterized insulin signaling and insulin receptor genetics in patients with severe insulin resistance and acanthosis nigricans, by establishing cell lines and characterizing their signaling properties. He then made the first discovery of mutations in the insulin receptor gene in patients with the Type A Syndrome of insulin resistance, and showed that these mutant receptors had abnormal signaling properties. Flier’s group also defined another the unique syndrome of insulin resistance, "insulin-mediated pseudoacromegaly," in which there is a defect in the ability of insulin and IGF-1 to activate glucose transport without mutations of the insulin receptor or GLUT 4 genes.

In the early 1990s, Flier saw the promise of transgenic technology and pioneered use of this technology in studies of diabetes and obesity. With Moller, he overexpressed normal or dominant negative insulin receptors in a tissue-specific manner in mice, thus creating models of increased sensitivity and insulin resistance, obesity, glucose intolerance and dyslipidemia. With Lowell, he created mice with deficiency of brown adipose tissue, establishing the role of brown adipose in energy metabolism in vivo in the rodent.

Perhaps his most important work was his contribution to the understanding of leptin and the pathways that it regulates. Along with Friedman, he provided the first demonstration that diet-induced obesity in rodents is associated with increased leptin expression, and that short-term starvation is associated with decreased leptin expression and blood levels. In a truly novel insight into the biology of leptin, Flier hypothesized and demonstrated that, when leptin levels fall during starvation, there is not only a powerful signal to the brain to stimulate hunger, but also regulation of the neuroendocrine axis for reproductive, thyroid, and adrenal control. His proposal that leptin serves as a switch from the fed to the starved state has been extremely influential and has fundamentally shaped the discourse of the field. Furthermore, he examined the role of leptin in the timing of puberty in mice and regulation of TRH neurons in the hypothalamus.

Flier’s group has also been at the forefront of the field of leptin signaling by the leptin receptor species, defining the role of SHP-2 in this process. Addressing the critical question of leptin resistance, Flier was the first to demonstrate that the suppressors of cytokine signaling could inhibit leptin signaling in hypothalamic target cells. He has also demonstrated a role for the blood brain barrier and defective signaling in nutritional obesity. With Elmquist, Flier defined the neural circuits regulated by leptin and demonstrated that leptin-activated neurons in the arcuate nucleus project to the lateral hypothalamus, where they contact melanin-concentrating hormone (MCH) and orexin neurons. In a very fruitful collaboration with his wife, Flier demonstrated that MCH was an important orexigenic hormone.

Most recently, Flier has used a transgenic approach to provide strong evidence that glucocorticoid reactivation in adipose tissue can produce a murine equivalent of the metabolic syndrome, with visceral obesity, insulin-resistant diabetes, hyperlipidemia, and hypertension. This model establishes the first plausible hypothesis for the genesis of this prevalent disorder.

In addition to his many scientific accomplishments, Jeff Flier is a remarkable mentor. His laboratory has served as a fertile training ground for many young investigators who themselves have gone on to lead distinguished careers. His ability to summarize and integrate information both in terms of his scientific thinking and his expertise as a lecturer are also truly remarkable. His accomplishments at building a first class endocrine unit at the Beth Israel Deaconess Medical Center and now to serve as Chief Academic Officer of that institution is another mark of important contributions to the field. His work has been recognized with a number of awards and honors, including the Eli Lilly Award of the American Diabetes Association, the Berson Lecture of the American Physiological Society, an Honorary Doctorate from the University of Athens, and election as a Fellow of the American Academy of Arts and Sciences.

Taken together, Jeffrey Flier is truly a leader in academic endocrinology whose work has created new insights into the pathogenesis of diabetes and obesity that have helped shaped the field.

C. Ronald Kahn


    Citation for the 2003 Clinical Investigator Award Lecture of The Endocrine Society to Dr. Elizabeth Barrett-ConnorGo
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Through application of rigorous epidemiologic study design and analysis Dr. Barrett-Connor has given us great insight into endocrine physiology and the role of hormones in disease pathogenesis. Dr. Barrett-Connor is a professor and Chief of the Division of Epidemiology in the Department of Family and Preventive Medicine at the University of California, San Diego School of Medicine. She received her bachelor’s degree from Mount Holyoke College and her M.D. degree from Cornell University Medical College, publishing her first paper, on traveler’s diarrhea, before graduation. After a residency in Internal Medicine and fellowship in infectious diseases, she obtained a postdoctoral degree from the London School of Hygiene and Tropical Medicine. A year later, in 1966, her first publication in the Journal of the American Medical Association appeared, an early indication of what was to be prolific publication in excellent journals.



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In 1972, Dr. Barrett-Connor shifted her focus of interest, founding the Rancho Bernardo Heart and Chronic Disease Study, which she still directs. This forward-thinking study enrolled 82% of the adult residents in Rancho Bernando, then a small town in Southern California, and followed them over time. It is fitting that Dr. Barrett-Connor receives this award at a meeting whose theme is cardiovascular endocrinology, as the Rancho Bernando study has contributed so much to this field. The study parsed the risk of cardiovascular disease between diabetics and nondiabetics, men and women, and estrogen-replacement users and nonusers. It was one of the first to delineate hyperlipidemia and diabetes as risk factors. The Rancho Bernardo study also demonstrated hormonal influences on other disorders, including osteoporosis and dementia. It evaluated the role of diet in development of hypertension and osteoporosis, clarified gender differences in risk factors and disease development, and allowed for correlation between lifestyle and health outcomes.

Dr. Barrett-Connor also has extensive experience as Principal Investigator (PI) or co-PI of multicenter clinical trials with direct implications for cardiovascular endocrinology. These include the Postmenopausal Estrogen/Progestin Interventions (PEPI) study, the Heart and Estrogen-Progestin Replacement Study (HERS), the Raloxifene Use in the Heart (RUTH) trial, and the Diabetes Prevention Program. While PEPI found that hormone replacement therapy improved lipid levels, HERS results indicated that estrogen use increased the risk of myocardial infarction and death in women with known disease. Dr. Barrett-Connor was a member of the Data and Safety Monitoring Board that recommended stopping the combined hormone replacement therapy arm of the Women’s Health Initiative because of an increased risk of breast cancer and cardiovascular events. The ongoing RUTH trial examines whether raloxifene has protective effects for women with known or high risk of heart disease.

Dr. Barrett-Connor’s interests have led to other large contributions, to the field of osteoporosis, as she has evaluated risk factors for osteoporosis and fracture, including thyroid hormone, androgens, gender, and diet and coffee intake. She has been a PI on the Multiple Outcomes of Raloxifene Evaluation (MORE) study, the Fracture Intervention Trial (FIT), and the National Osteoporosis Risk Assessment (NORA). The MORE study found that raloxifene reduced bone loss and the risk of new vertebral fractures in women with osteoporosis and identified a 75% reduction in invasive breast cancer and a 40% reduced risk of cardiovascular disease in the women who were at highest risk. The Continuing Outcomes Relative to Evista study is evaluating whether these effects persist long term. The FIT found that alendronate significantly reduced spine and hip fractures in older women who had prior fractures or osteoporosis by bone densitometry. This study has been extended by 3 yr to determine what happens to bone density in women who continue or stop alendronate. The ambitious NORA, a longitudinal, observational study of 200,000 postmenopausal women, is examining fracture risk by various characteristics including use of hormone replacement therapy.

Dr. Barrett-Connor has published more than 600 publications in esteemed journals, including 19 papers in the New England Journal of Medicine and the Lancet, and 27 papers in the Journal of the American Medical Association. She is or has been a member of FDA Expert Advisory Committees, the National Institute of Aging Advisory Board, and NIH Consensus Development Committees on Osteoporosis and Hormone Replacement Therapy. She has received numerous awards from the international community in recognition of her work and is a member of the Institute of Medicine.

But the story is not finished, as Dr. Barrett-Connor continues to be involved in additional studies evaluating the role of exogenous dehydroepiandrosterone and phytoestrogens on coronary heart disease risk factors and osteoporosis, and the factors that influence osteoporosis in aging men. We honor this consummate clinical investigator for her contributions to date, and eagerly await the next chapters in this saga.

Lynnette K. Nieman


    Citation for the 2003 Gerald D. Aurbach Award Lecture of The Endocrine Society to Dr. Gilbert VassartGo
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The recipient of the 2003 Gerald D. Aurbach Lecture Award is Dr. Gilbert Vassart, Professor of Medical Genetics and Director of the Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (IRIBHM) of the University of Brussels, Belgium, and Head of the Department of Medical Genetics at Erasmus Academic Hospital. Vassart received his medical degree, summa cum laude, in 1969, and his Ph.D. in 1974 from the University of Brussels, with an intervening year of residency in internal medicine at the St. Pierre Hospital in Brussels. His thesis work on the study of protein synthesis in eukaryotes was performed at the IRIBHM, then directed by Professor Jacques Dumont. He remained at the IRIBHM for postdoctoral training, becoming an established investigator in 1979, Vice Director of the Institute in 1992, and Director in 2001.



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The central theme of Vassart’s work, spanning his career from graduate work until the present, has been the creative application of molecular biologic methods to the study of hormone synthesis and action. His pioneering use of molecular genetics in endocrinology has also had a profound impact on the fields of signal transduction and molecular pharmacology. His first major accomplishment was the isolation of the 8400-base thyroglobulin mRNA, which he undertook as a novel approach to determining the structure of the protein critical for thyroid hormone generation. In collaboration with Sam Refetoff, he purified the mRNA for prolactin and demonstrated transcriptional control of prolactin and GH by estrogens and thyroid hormone, respectively. He was the first to clone and sequence the thyroglobulin cDNA, and he identified loss of function mutations in the genes for thyroglobulin and thyroperoxidase, a key enzyme in thyroid hormone synthesis, as the cause of congenital goiter in animal models and humans.

Given the central importance of the TSH receptor for understanding the mechanism of action of TSH and the basis for Graves and other thyroid diseases, there was intense competition to clone this G protein-coupled receptor’s cDNA. Vassart and his colleagues noted that, for the few G protein-coupled receptors cloned up to then (primarily monoamine receptors), there is relative conservation of amino acid sequence in several of the transmembrane helices. In a brilliant stroke, they used degenerate primers corresponding to these conserved sequences to allow PCR-amplification of novel members of the G protein-coupled receptor family. The landmark paper in Science describing this work in 1989 was followed by an equally important Science paper that same year using this approach to clone the TSH receptor cDNA. The first paper at once revealed the potential size and diversity of the G protein-coupled receptor family while also populating this family with "orphans" whose agonists and physiologic function were unknown. Vassart, in collaboration with others, made major inroads in characterizing such orphans, including for example, identification of adenosine, serotonin, odorant, and chemokine receptors. The latter proved particularly significant as, with his collaborators, he identified a mutation of the CCR5 chemokine receptor that confers resistance to HIV in homozygous humans.

Gilbert Vassart’s work has dramatically advanced our understanding of the molecular basis, not only of human thyroid diseases, but more generally of disorders of signal transduction involving G protein-coupled receptors. A superb molecular biologist, he is also a medical geneticist responsible for introducing the use of molecular genetics for prenatal diagnosis in Belgium in 1983. He truly defines what it means to be a physician-scientist.

Allen M. Spiegel


    Citation for the 2003 Sidney H. Ingbar Distinguished Service Award of The Endocrine Society to Dr. Robert B. JaffeGo
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A Michigan native, Bob Jaffe received his undergraduate and medical education at the University of Michigan. He was an internal medicine fellow in endocrinology and an obstetrics and gynecology resident at the University of Colorado. During a postdoctoral fellowship in reproductive endocrinology at Stockholm’s Karolinska Sjukhuset, he initiated the studies of feto-placental endocrinology that have remained a focus throughout his career. Bob returned to Michigan, where he quickly rose to professor, directed the Steroid Research Unit, and codirected the Reproductive Endocrinology Program. Subsequently, he became Professor and Chair of the Department of Obstetrics, Gynecology and Reproductive Sciences at the University of California, San Francisco and founder and Director of the Center for Reproductive Sciences. He remains on the faculty almost 30 yr later.



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FIG. 7.
 
Bob’s service to endocrinology spans every aspect of the discipline. His abiding passion for training physician-scientists has benefited over 60 former postdoctoral fellows. That passion is also reflected in his directorship of the NICHD Reproductive Scientist Development Program, which trains outstanding obstetrician-gynecologists for academic careers in molecular and cellular biology.

Bob has published well over 300 original articles, book chapters, and books, including the influential textbook, Reproductive Endocrinology: Physiology, Pathophysiology and Clinical Management, which he coauthored with Samuel S. C. Yen 25 yr ago and is now in its fourth edition. His basic and clinical research in humans and other animals, supported continuously for over 30 yr, including an NIH Merit Award, has addressed adrenal, ovarian, and testicular steroidogenesis in the placenta and fetus and steroid function, regulation, and metabolism in placental, gonadal, and other fetal and adult tissues. Of particular interest are his studies, with Rees Midgley, of regulation of gonadotropin synthesis, secretion, and action during adrenarche, puberty, and, particularly, the menstrual cycle. His studies of dose- and time-related gonadal steroid modulation of the pituitary gonadotropin secretory response to GnRH and of GnRH agonistic and antagonistic effects on pituitary-ovarian function are also noteworthy. Bob studied regulation of prolactin secretion in the normal pituitary and prolactinomas and the effects of hyperprolactinemia on pituitary secretory function. He made seminal contributions to our understanding of the regulation of fetal anterior pituitary, adrenomedullary, adrenocortical, and gonadal development and function by hypothalamic releasing factors, pituitary hormones, and several growth factors in humans and other primates. Recently, he has directed his attention to the role of angiogenesis and vascular permeability in normal reproductive physiology and in the initiation, progression, metastasis, and treatment of ovarian cancer.

Bob has been a member of more than a score of local, state, and federal medical and scientific societies, advisory boards, study sections, and foundations and has served as director or president of seven of them. He served 3 yr on The Endocrine Society Council and almost 5 yr as Secretary-Treasurer, resigning to assume his current role as President of the Hormone Foundation, which Bob and his Board of Directors have made an increasingly effective vehicle for increasing public awareness of endocrine-related disorders and the importance of endocrinologists, medical research, and The Endocrine Society. Beginning with women’s health issues, they are developing educational programs in prostate disease, hormone abuse, the metabolic syndrome, and other disorders.

Bob has been recognized by the American College of Obstetrics and Gynecology with its Purdue Frederick Award for Excellence in Medical Research, the Society for Gynecologic Investigation’s President’s Distinguished Scientist Award and its President’s Mentor Award, the American Society for Reproductive Medicine’s Distinguished Scientist Award, memberships in the Association of American Physicians and the Institute of Medicine, and fellowship ad eundum in the Royal College of Obstetricians and Gynaecologists.

Bob Jaffe is an elegant, gracious, articulate ... and very disciplined man. He and his wife Evelyn live on Mt. Tiburon, overlooking the Bay across the Golden Gate from San Francisco, and for many years Bob has biked to and from work. He is also a multitalented man, having, for example, designed his handsome contemporary home with his talented wife Evie and incorporated wonderful works of art into it.

Bob puts his family high on his list of priorities. Evie is an occupational therapist and a creator of beautiful jewelry and ceramics. Their son Glenn and daughter-in-law Linda are professors on the medical faculties of Duke and the University of North Carolina; their marriage thrives largely because of Glenn’s fanaticism about, and Linda’s antipathy toward, college basketball. Their artistic daughter Terri is a floral designer in the San Francisco Bay Area, and her proximity to Tiburon gives Evie and Bob the opportunity to spend many hours with their granddaughter Aliya.

David N. Orth


    Citation for the 2003 Roy O. Greep Award Lecture of The Endocrine Society to Dr. Richard P. LiftonGo
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Roy Greep, M.D., would be particularly pleased with this year’s winner of the award that bears his name. Richard P. Lifton, M.D., Ph.D., received his undergraduate training in biology from Dartmouth College followed by the Medical Science Training Program at Stanford University, where he received his M.D. and Ph.D. It was in the laboratory of Dr. David Hogness that he received the fundamental molecular biology training that has allowed him to pursue his career in genetics.



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FIG. 8.
 
Dr. Lifton returned to the East Coast to complete a medical residency at Brigham and Women’s Hospital (BWH), where he also served as Chief Medical Resident. During this time, he solidified his career goal of applying his molecular biology training to the study of human genetic diseases. During the next 6 yr, he submerged himself in the genetics of human hypertension, first as a fellow, then as an instructor, and finally as an Assistant Professor in the Endocrine-Hypertension Division at BWH and Harvard Medical School.

The approach that he used in identifying the first genetic mutation involved in hypertension—glucocorticoid-remediable aldosteronism (GRA)—is reflective of his philosophy of using genetics to better understand physiology. In his GRA studies, he collaborated with Dr. Robert Dluhy in Boston, who had collected a large GRA pedigree, and with Dr. Jean-Marc Lalouel in Salt Lake City, who had extensive experience identifying genetic mutations. In a series of elegant experiments, he determined that the molecular basis for this disease was the formation of a fusion gene containing the regulatory region of 11-hydroxylase and the coding region for aldosterone synthase. Identifying this mutation also provided the basis for understanding the pathophysiologic characteristics of GRA.

In 1994, Dr. Lifton joined the Department of Genetics and the Howard Hughes Medical Institute at Yale and has risen through the ranks to assume the position of Director of the Yale Center for Human Genetics and Genomics and Chair and Professor in the Department of Genetics. Dr. Lifton’s laboratory has continued to use molecular genetic analyses to dissect physiologic processes that regulate cardiovascular and renal function in humans, with an emphasis in blood pressure regulation. By coupling characteristics of hundreds of families from around the world with human genetic studies, his group has mapped over 30 human disease genes and has identified functional mutations underlying more than 20. These studies have provided new insights into the mechanisms underlying hypertension, stroke, osteoporosis, and ion disorders. Most significantly, by the study of families with rare Mendelian forms of severely high or low blood pressure, his laboratory has identified mutation of six genes that raise blood pressure and eight genes that lower blood pressure. All mutations modify net salt balance and thereby change blood pressure in humans. Dr. Lifton’s research also has identified new targets and pathways for the development of novel therapeutic agents that may be applicable to the general hypertensive population. For example, the WNK kinase genes identify a previously unrecognized signaling pathway in the regulation of blood pressure in humans.

Similarly, his work on magnesium homeostasis has identified mutations in a novel gene, paracellin-1, that is required for paracellular flux in magnesium in the thick ascending limb of Henley. Finally, recent work has identified mutations in the Wnt signaling pathway that resulted in a marked increase in bone density, providing a novel target for the development of agents that promote bone formation.

Dr. Lifton has received numerous awards for his research, including the Homer Smith Award of the American Society of Nephrology, the Novartis Award for Hypertension Research of the American Heart Association, and the Medical Research Award of the Pasarow Foundation. He also has been elected to the Association of American Physicians, the National Academy of Science, and the Institute of Medicine. Finally, Dr. Lifton serves as chair of the NIH Advisory Committee for Large-Scale Genomic Sequencing, and is a member of the National Advisory Council for the National Human Genome Research Institute.

In addition to his outstanding body of research, Dr. Lifton remains thoroughly committed to providing outstanding training to new fellows and students, having served as a mentor to many over the past decade. Through his personal research activities and his training of new students, he serves as a role model for the appropriate application of basic science techniques to human disease.

Based on this outstanding record of achievement, it gives me great pleasure to report the selection of Richard P. Lifton, M.D., Ph.D., as the recipient of the Roy O. Greep Lecturer Award for 2003.

Gordon H. Williams


    Citation for the 2003 Distinguished Educator Award of The Endocrine Society to Dr. Leslie J. DeGrootGo
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Dr. Leslie J. DeGroot is the recipient of the 2003 Distinguished Educator Award of The Endocrine Society. The Distinguished Educator Award is presented in recognition of exceptional achievement as an educator in the discipline of endocrinology. Dr. DeGroot has indeed made extraordinary educational contributions to our field as the developer and editor of major authoritative textbooks, including The Thyroid and Its Diseases, now in its sixth edition, and the encyclopedic Endocrinology, now in its fourth edition. The Thyroid and Its Diseases is the primary reference textbook of thyroidology and has been a major instrument in the training of endocrine specialists worldwide. The three-volume Endocrinology provides a complete, extensive, and up-to-date analysis of endocrine disease and basic endocrine physiology from internationally known experts. Every aspect of endocrinology is covered in significant detail by an authority in the field. A clinical focus emphasizes diagnosis and therapy, diagnostic methods, and the pharmaceutical therapies used in treatment. These volumes are an outstanding reference source for clinicians and basic scientists alike. While the textbooks edited by Dr. DeGroot have their place in the library of every academic medical center and in the office of all who have an expert interest in endocrinology, his educational efforts have not remained limited to printed work. Leslie DeGroot indeed quickly recognized the tremendous potential of the world wide web as a source of medical information and created the web site "Thyroid Disease Manager," which provides physicians, researchers, trainees, and patients around the world with a current, complete, objective, free, and downloadable source of information. Physicians around the world have access to this outstanding online reference textbook at any time. More recently, Leslie DeGroot created a second web site named "Endotext" that is already getting thousands of hits daily and intends to be the premier provider of accurate and well-organized web-based clinical endocrine information. Finally, whereas Dr. DeGroot’s contributions to the development of printed and online reference textbooks for our field have been exceptional, it is important to also remember that, in the course of a long and productive career as a researcher as well as a clinician, Leslie DeGroot has trained numerous fellows who have gone on to successful academic careers in the United States and abroad. For his efforts in education and training, Leslie DeGroot is widely regarded a one of the "fathers" of the field of modern thyroidology.



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Dr. DeGroot attended Union College and received his M.D. degree from the Columbia College of Physicians and Surgeons. After internship and residency at the Columbia Presbyterian Hospital in New York City, he worked at the National Cancer Institute and then did an endocrinology fellowship with Dr. John Stanbury at the Massachusetts General Hospital. He became a faculty member at Harvard Medical School in 1959 and then moved to the Massachusetts Institute of Technology in 1966. He was recruited to the University of Chicago in 1968 and rapidly achieved his current position of Professor of Medicine and Director of the Thyroid Study Unit. As a scientist, Dr. DeGroot has made important research contributions to a wide spectrum of topics in the field of thyroidology. These include the understanding of thyroid hormone synthesis and its mechanism of action, iodine metabolism, thyroid cancer, and autoimmune thyroid disease. He has authored more than 450 original research articles. His current research interests focus on the development of innovative treatment of metastatic thyroid cancer with adenoviral vectors using cell-specific expression of toxic gene products. He is also actively involved in elucidating the molecular genetics of Graves’ disease.

Dr. DeGroot has been the recipient of numerous awards and distinctions, including the Distinguished Service Award as well as the Distinguished Research Award from the American Thyroid Association. He was also president of the American Thyroid Association in 1973 and served as member of the Executive Council of The Endocrine Society from 1989–1991. Leslie DeGroot is an honorary fellow of the British Royal Society of Medicine and of the Japanese Endocrine Society. In 1998, he was the recipient of the Columbia University Medical Alumni Gold Medal for Outstanding Academic Achievement.

Leslie DeGroot’s stamina, energy, hard work, and acumen are legendary to all who have worked around him. Our field is greatly indebted to his extraordinary contributions to the development of major tools for the dissemination of knowledge in endocrinology. It is therefore highly appropriate that we honor Dr. DeGroot with the Distinguished Educator Award of The Endocrine Society.

Dr. Van Cauter


    Citation for the 2003 Distinguished Physician Award of The Endocrine Society to Dr. Arlan L. RosenbloomGo
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Dr. Arlan L. Rosenbloom, Distinguished Service Professor Emeritus of Pediatrics at the University of Florida, is internationally recognized as a pioneer of pediatric endocrinology and diabetology, a prolific educator and mentor, an innovative developer of programs for children with diabetes and other endocrine disorders, and a wide-ranging, highly productive clinical investigator, reflected in his nearly 300 articles and 60 chapters and books in the past 38 yr.



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He started the pediatric endocrinology program at Florida in 1968, developing the team approach to pediatric diabetes care comprising 24-h availability and outpatient management of newly diagnosed patients at a time when such patients were hospitalized for extended periods, and published data on the cost benefits and efficacy. He built Florida’s camps for children with diabetes as an extension of the academic endeavor and as the philosophic nidus of the pediatric diabetes program providing incomparable opportunities for patient education and motivation, health science student and trainee education, and clinical research; the state-funded regional program for children with diabetes and other endocrine disorders covering over one third of the State; and a unique residential unit for psychosocial rehabilitation of children with diabetes. He directed the University of Florida General Clinical Research Center from 1974–1980. He has served on numerous NIH and FDA review bodies, task forces, and site visit teams. He chaired the workgroup of the National Diabetes Commission in 1974 that developed the recommendation to form the National Diabetes Data Group, and the American Diabetes Association Workgroup that developed the consensus statement on Type 2 Diabetes in Children. He has also served on numerous committees of endocrine and diabetes professional societies, and on many editorial boards, including The Journal of Clinical Endocrinology & Metabolism. He has reviewed grant proposals for research foundations and institutions in the United States, England, Ireland, and Israel.

Dr. Rosenbloom’s vision and leadership were prominent in the movement of diabetes into the mainstream of pediatric endocrinology. He organized the first conference of pediatric diabetologists in 1970 around the issue of what was then termed "chemical diabetes," which was published in summary in Diabetes and as full proceedings in Metabolism, and he later initiated satellite diabetes programs for the Lawson Wilkins Pediatric Endocrine Society that are now integral.

Dr. Rosenbloom is the ultimate clinical investigator, with uncanny ability to identify and appreciate the significance of clinical findings that others have missed, and carefully document his observations. Similarly, he has often questioned prevailing wisdom and practices and pursued studies to challenge them. As a fellow, he did an epidemiologic analysis that led him to markedly revise the accepted estimate of incidence of congenital adrenal hyperplasia (CAH) from 1 in 64,000 to 1 in 10,000, a figure close to that confirmed in screening studies decades later. He also described the concurrence of non-salt-losing and salt-losing forms of CAH within families at a time when it was thought that these were genetically separate conditions. He published one of the earliest papers on GH treatment. He early reported normal intellect and achievement with GH deficiency and 35 yr later, in controlled studies, with normal short stature. During his 1974–1975 sabbatical with Sam Goldstein at McMaster, he described insulin receptors in cultured fibroblasts correlating with donor age (Science 1976), and normal insulin binding to fibroblasts in lipoatrophic diabetes. His were the first observations of elevated insulin levels in what is now considered impaired glucose tolerance, and potential long latency for the development of type 1 diabetes in children based on 10- to 12-yr follow-up studies. He was also the first to document increased insulin responses during normal adolescence. He discovered the complication of limited joint mobility in childhood diabetes and described its prevalence, natural history, and associations with growth impairment, increased risk for microvascular disease, and relationship to long-term glycemic control, and he recently reported marked decrease in frequency and severity resulting from improved management over the past 20 yr. He compiled and analyzed the highly influential report on the then most extensive series of cerebral edema complicating diabetic ketoacidosis. He recruited a team of researchers with whom he described novel clinical features, epidemiology, genetics, biochemistry, psychosocial status, and treatment of a unique population with GH receptor deficiency in the Ecuadorian Andes, comprising approximately one third of all known cases and including the entire age span. He has published analyses of pediatric and pediatric endocrine practice spanning 25 yr.

His awards include the faculty research prize of the University of Florida College of Medicine in 1994, the Distinguished Alumnus Citation of the University Of Wisconsin in 1995, and the Florida Blue Key Distinguished Faculty Award in 1995.

Janet H. Silverstein


    Citation for the 2003 Richard E. Weitzman Memorial Award of The Endocrine Society to Dr. Ana Claudia LatronicoGo
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The 2003 recipient of the Richard E. Weitzman Award from The Endocrine Society is Dr. Ana Claudia Latronico, a physician/scientist from São Paulo, Brazil. Dr. Latronico received her M.D. in 1987 from the Faculdade de Ciências Médicas de Santos in the state of São Paulo, Brazil. In 1991, Dr. Latronico began her research fellowship in Endocrinology in the Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo in the laboratory of Dr. Berenice B. Mendonca. It was there that Dr. Latronico first developed an interest in the genetic basis of endocrine disorders. To receive further training in this area, Dr. Latronico came to the United States to spend 2 yr in the laboratory of Dr. George P. Chrousos at the NIH. With Dr. Chrousos’ group, Dr. Latronico documented some of the first inactivating mutations of the ACTH receptor gene associated with isolated glucocorticoid deficiency and inactivating mutations of the LH receptor gene associated with ovarian and testicular resistance to LH. Dr. Latronico was awarded her Ph.D. from the University of São Paulo in 1995 and continued her studies as a postdoctoral fellow with Dr. Mendonca. Since 2001, she has been a Professor in the Endocrinology Division of the School of Medicine at the University of São Paulo, where she has continued to make major contributions toward deciphering the genetic basis of endocrine diseases.



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FIG. 11.
 
Brazil has offered a unique opportunity to study the genetic basis for endocrine disorders due to its complex and heterogeneous genetic background. Also, due the small number of specialized medical centers, one observes a "funnel" effect, where individuals having endocrine disorders are referred to just a few centers, the University of São Paulo being one of them. Yet, the location has also been a challenge given the much more limited resources available for research. It is therefore to Dr. Latronico’s and Dr. Mendonca’s credit that they have built up an internationally recognized center for the identification of novel mutations of genes associated with endocrine diseases. Dr. Latronico’s research, which so elegantly bridges the clinical and basic spheres of endocrinology, has served to help define the functional roles of particular genes in normal and pathophysiological endocrinology.

In the course of her studies, Dr. Latronico has identified several activating and inactivating mutations of the LH receptor. The inactivating LH receptor mutations, identified in males with pseudohermaphroditism due to Leydig cell hypoplasia and then screened for in their female siblings with infertility, have served to underscore the role of proper folding of cell surface receptors because many of these mutations result in a loss of target cell responsiveness due to the retention of misfolded mutant receptors intracellularly. Activating mutations of the LH receptor, in turn, have identified residues involved in key interactions between helices that serve to stabilize the receptor in the basal state. In addition, Dr. Latronico has also led or has been involved in a number of other studies examining several different endocrine systems. Examples of such studies include: identifications of a mutation in the SRY gene associated with partial gonadal dysgenesis, a mutation of the vitamin D receptor gene associated with hereditary 1,25-dihydroxyvitamin D3-resistant rickets, mutations in the type II 3ß-hydroxysteroid dehydrogenase gene associated with female premature pubarche, a mutation of the gsp gene as a putative cause of Leydig cell tumors, a mutation in the androgen receptor associated with partial androgen insensitivity syndrome, mutations in the GnRH receptor gene associated with hypogonadotropic hypogonadism, a mutation of the DAX-1 gene associated with X-linked adrenal hypoplasia, a mutation of the p53 gene associated with sporadic adrenocortical tumors, and a mutation of the glucocorticoid receptor associated with pseudohermaphrotidism in females. These studies have been significant for establishing a functional link between a given gene and a given endocrine disorder. Whereas in some cases these links may have been obvious, in many other cases it has taken a keen knowledge of clinical and basic endocrinology to hypothesize such a connection. In addition, because the mutations thus identified are structure/function studies performed by nature, they have often provided insights into the structural basis for the gene product’s mechanism of action.

In recognition of these outstanding accomplishments in research, The Endocrine Society is pleased and honored to grant Dr. Ana Claudia Latronico its 2003 Richard E. Weitzman Award.

Deborah L. Segaloff


    Citation for The Endocrine Society and Pfizer, Inc. International Award for Excellence in Published Clinical Research in The Journal of Clinical Endocrinology & Metabolism
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First Prize

"The Cardiovascular Risk of GH-Deficient Adolescents." Vol. 87, No. 8, 2002, pp. 3650–3655. Authors: Annamaria Colao, Carolina Di Somma, Mariacarolina Salerno, Letizia Spinelli, Francesco Orio, and Gaetano Lombardi. Departments of Molecular and Clinical Endocrinology and Oncology (A.C., C.D.S., F.O., G.L.), Pediatrics (M.S.), and Internal Medicine I (L.S.), University Federico II of Naples, 80131 Naples, Italy.

First Prize

"Adrenal Incidentaloma: A New Cause of the Metabolic Syndrome?" Vol. 87, No. 3, 2002, pp. 998–1003. Authors: Massimo Terzolo, Anna Pia, Anna Alì, Giangiacomo Osella, Giuseppe Reimondo, Silvia Bovio, Fulvia Daffara, Massimo Procopio, Piero Paccotti, Giorgio Borretta, and Alberto Angeli. Dipartimento di Scienze Cliniche e Biologiche (M.T., A.Al., G.O., G.R., S.B., F.D., P.P., A.An.), Medicina Interna I,A.S.O. San Luigi, 10043 Orbassano, Italy; and Università di Torino, 10043 Orbassono (TO), and Endocrinologia, A.O. Santa Croce e Carle, 12100 Cuneo (A.P., M.P., G.B.), Italy.

Finalist

"The Effects of Varying Doses of T on Insulin Sensitivity, Plasma Lipids, Apolipoproteins, and C-Reactive Protein in Healthy Young Men." Vol. 87, No. 1, 2002, pp. 136–143. Authors: Atam B. Singh, Stanley Hsia, Petar Alaupovic, Indrani Sinha-Hikim, Linda Woodhouse, Thomas A. Buchanan, Ruoquing Shen, Rachelle Bross, Nancy Berman, and Shalender Bhasin. Division of Endocrinology, Metabolism, and Molecular Medicine, Charles R. Drew University of Medicine and Science (A.B.S., S.H., I.S.-H., L.W., R.S., S.B.), Los Angeles, California 90059; Oklahoma Medical Research Foundation (P.A.), Oklahoma City, Oklahoma 73104; University of Southern California School of Medicine (T.A.B., R.B.), Los Angeles, California 90059; and Harbor-University of California-Los Angeles Medical Center (N.B.), Torrance, California 90502.

Finalist

"Narrow Individual Variations in Serum T4 and T3 in Normal Subjects: A Clue to the Understanding of Subclinical Thyroid Disease." Vol. 87, No. 3, 2002, pp. 1068–1072. Authors: Stig Andersen, Klaus Michael Pedersen, Niels Henrik Bruun, and Peter Laurberg. Department of Endocrinology (S.A., N.H.B., P.L.) and Clinical Biochemistry (K.M.P.), Aalborg Hospital, Aalborg DK-9000, Denmark.


    Footnotes
 
Photos of the winners will be available after the annual meeting of The Endocrine Society and will be published in a future issue.





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