THE ENDOCRINE
Citation for the Fred Conrad Koch Award Endocrine Society to Melvin M. Grumbach Selna L. Kaplan
of The and
The Endocrine Society is pleased to bestow its most prestigious honor, the Fred Conrad Koch award, on that dynamic duo of pediatric endocrinology, Melvin M. Grumbach and Selna L. Kaplan. Mel and Selna have collaborated for 35 yr, influencing much of our understanding of pituitary physiology, growth, puberty and neuroendocrinology, and virtually every aspect of pediatric endocrinology. Mel got off to a quick start, with an M.D. from Columbia University in 1948 at the tender age of 22, and he completed his fellowship with the legendary Lawson Wilkins in 1955.
993
Like many of us, Mel was always interested in sex. While with Wilkins he began his studies of sex chromatin and its various disorders in hermaphroditism and of the disorders of adrenal steroid synthesiscausing pseudohermaphroditism. Upon moving back to Columbia University to head the newly formed division of Pediatric Endocrinology, Mel continued his landmark studies of sex chromatin, showing that all human X chromosomesin excessof one replicated late and proving that late replication caused heterochromatinization and formation of sex chromatin (the Barr body). He advanced the fixed differentiation hypothesis of X chromosomebehavior independently of Mary Lyon (but somehow the term “Grumbachianization” of sex chromatin never caught on). He showed that the second X chromosome was not completely inactive, and that geneson the second X chromosome were necessaryfor normal ovarian development. He and his colleaguescorrelated karyotypes and phenotypes in sex chromosomeabnormalities, leading to his independent discovery of the discordance between phenotype and sex chromatin pattern in Turner and Klinefelter syndromes. Obviously things were going well for Mel, but his research effort made a quantum leap forward in 1958 when Selna Kaplan joined Mel as one of his first postdoctoral fellows. Selna was also a native New Yorker but had taken a longer course before returning home. Crowded with returning veterans on the GI bill, the medical schools of the late 1940s did not welcome women with open arms. Selna outfoxed them by first going to graduate school, earning her Ph.D. in Anatomy from Washington University (St. Louis) in 1953 and her M.D. from the same*institution in 1955. When Selna joined Mel’s ‘lab, two really hot fields were just beginning to make their mark in endocrinology. First, Bersonand Yalow were developing immunoassaytechnology uptown at the Bronx VA Hospital. Second, new techniques
Downloaded from https://academic.oup.com/endo/article-abstract/131/2/993/2496343 by East Carolina University user on 16 January 2019
in studies of PTH and the PTH-related peptide. His group developed models for the three-dimensional structures of the receptor-binding portions of these molecules that gave insight into how these two molecules could bind to the same receptor in spite of a significant lack of homology in important portions of the molecules. Aspects of the models were confirmed by spectroscopic analyses. The group has used these models to design novel antagonists and agonists with potential pharmacological usefulness. More recently, Cohen and McKerrow have demonstrated further the power of structural biology methods for designing novel pharmaceuticals in their studies of an elastase which the water-borne cercariae of schistosomes secrete to bore through the foot pad of the host and enter the lymphatic system and ultimately the liver. They constructed a threedimensional model of the elastase and designed mechanismbased inhibitors that block both elastase activity and infectivity of the organism in ho. Fred has been a member of The Endocrine Society since 1989. Additional indications of his impact are reflected by his numerous invitations to speak at major meetings such as the American Chemical Society, American Physical Society, ICN/UCLA Symposia, and the National Academy of Sciences, service on the NIH Biophysics and Biochemical Chemistry Study Section, service on the editorial boards of the Journal of Molecular Biology and Protein Engineering, and receipt of NIH grants and a program grant from the Defense Advanced Research Project Agency. He currently supervises eight postdoctoral fellows and graduate students and is widely sought after by biotechnology and pharmaceutical companies as a consultant on drug design. While developing a program in research with international impact, Fred has also developed into one of UCSF’s most sought-after teachers who is equally comfortable on the medical wards reviewing problems in endocrinology or general internal medicine, or in the basic departments. He is respected by his colleagues as an excellent clinical endocrinologist and internist and as such defies the trend of the disappearing triple threat. Fred thus represents an unusual combination of clinical endocrinologist and structural biochemist who is at the forefront of a technology that is likely to have even greater impact on endocrinology in the future. The Endocrine Society is proud to award him the Richard E. Weitzman Award.
SOCIETY
994
THE ENDOCRINE
Endo - 1992 Voll31 . No 2
largely in Endocrinology; number 26 in this series appeared in December 199 1. Beyond these and a great number of other achievements in clinical endocrinology and whole animal physiology, perhaps Mel and Selna’s greatest impact has been through the people they trained. Over 80 postdoctoral fellows and visiting scientists learned from and worked with Mel and Selna. Over 35 of these now head their own laboratories, 26 are professors, and 10 chair departments of pediatrics. Both have vigorously championed the rights of children, stringent review of clinical experimentation, and careful consideration of the social impact of medical technology. In an era of premature enthusiasm and media hype, they have been the voice of restraint in the use of biosynthetic hGH for treating short healthy non-GH deficient children. This unmatched record of achievement in endocrinology and pediatrics has not gone unnoticed. Although a detailed list of all their awards and honors would take many pages, a few highlights include the following. Both have served as president of the Lawson Wilkins Pediatric Endocrine Society, Selna has served as president of the Western Society for Pediatric Research, and Mel served as president of The Endocrine Society in 1984. They have served on NIH study sections and councils and on innumerable national advisory boards in endocrinology and pediatrics, served on about a dozen editorial boards of journals, and have been elected to dozens of national and international societies. Our society previously honored Mel with the Robert H. Williams Leadership Award in 1980 and honored Selna with the Ayerst Service Award in 1987. Mel is also a member of the Institute of Medicine of the National Academy of Sciences and received an honorary doctorate from the University of Geneva in 1991. Thus, in view of this long record of outstanding achievement in basic and clinical research, of service to science,
Downloaded from https://academic.oup.com/endo/article-abstract/131/2/993/2496343 by East Carolina University user on 16 January 2019
in protein purification, pioneered by the late C. H. Li, led to the isolation of most of the pituitary hormones in pure form. Mel and Selna quickly mastered these new technologies. They were among the first to use human GH (hGH) RIA to delineate the roles of hGH in various disorders of growth, and they were the first to show that the whole hGH molecule was needed for activity, when most thought a small core peptide sequence would suffice. They developed RIAs for other hormones, including LH, FSH, TSH, and PRL. Not content just to measure hormones, they codiscovered one of their own-human chorionic somatomammotropin (sometimes termed placental lactogen)-and described its GH-like activity and its first RIA. In 1966 Mel and Selna followed Horace Greeley’s advice and headed west. Mel had been appointed Chairman of Pediatrics at the University of California, San Francisco, and Selna took over the operation of the pediatric endocrine research laboratory. Their new environment proved even more productive than the old. Based on incisive analysis of TRH-induced changes in PRL concentrations, Mel and Selna were the first to show that the overwhelming majority of children with idiopathic hypopituitarism or isolated GH deficiency had a hypothalamic, rather than a pituitary disease. They have always been leaders in the scientific investigation of disorders of growth and the use and effects of GH, publishing dozens of widely cited papers in this field. They defined the syndromes of neonatal hypopituitarism with hypoglycemia, of septo-optic dysplasia, and of hypopituitarism as a consequence of central nervous system (CNS) irradiation When the mini-epidemic of Creutzfeld-Jacob disease in recipients of pituitary-derived GH was discovered, the pediatric endocrine community turned to Selna Kaplan for guidance. As chairman of the Growth Hormone Subcommittee and president of the Lawson Wilkins Pediatric Endocrine Society, she worked with NIH officials to gather data and inform patients and provided a perspective and a firm, logical hand in the face of exaggerated fears, claims, and counterclaims. As principal investigator of the first national trial of hGH made by recombinant DNA technology she greatly facilitated the expeditious approval of biosynthetic hGH to replace pituitary hGH. Using exquisitely sensitive RIAs for gonadotropins and sex steroids, Mel and Selna painstakingly described the hormonal changes in normal infants and in children in puberty. They described the striking rise of LH in response to GnRH that precedes clinical signs of puberty and demonstrated the increasing insensitivity of sex-steroid feedback on the hypothalamus as puberty advances. They discovered that puberty is restrained in normal children by the CNS rather than by sex steroids and showed that it was the waning of this CNS inhibition that initiates puberty. They showed that the onset of adrenarche is independent of puberty and were among the first to describe the use of GnRH agonists in the treatment of precocious puberty. Beginning in the late 1970s they initiated work with the chronically catheterized sheep fetus, a technically demanding but powerful physiological system for delineating the developmental endocrinology of the third trimester mammalian fetus. This led to their continuing series of papers, “Hormone ontogeny in the ovine fetus,” published
SOCIETY
THE ENDOCRINE
SOCIETY
995
medicine, and society, and in training the next generation of endocrinologists, The Endocrine Society bestows the 1992 Fred Conrad Koch Award on Melvin M. Grumbach and Selna L. Kaplan. Citation
Lectureship 0. Thorner
of The
The Endocrine Society has selected Michael 0. Thorner, M.B., B.S., DSc., Professor of Medicine, Chief of the Division of Endocrinology, and Director of the General Clinical Research Center at the University of Virginia, as the recipient of the 1992 Edwin B. Astwood Lectureship for Scientific Achievement. This selection recognizes his outstanding contributions to clinical and basic research in neuroendocrinol%Y* Dr. Thorner was born in Beaconsfield, west of London, UK, and received his M.B., B.S. with honors, in 1970 from the Middlesex Hospital at the University of London. Clinical training followed the English pattern with internship and residency in a wide spectrum of subspecialties at several London hospitals. A long-standing interest in endocrinology was pursued by fellowship with Michael Besserand subsequent appointment as Lecturer in Medicine at St. Bartholomew’s, one of the major endocrine training centers in the UK. During this time, Dr. Thorner developed his interest in neuroendocrinology, and he played a major role in establishing the basic physiology and clinical applications of somatostatin. This work established the clinical effects of somatostatin in the gastrointestinal tract and on GH secretion, and was the forerunner of the current use of long-acting somatostatin analogsin the treatment of acromegaly. This interest in GH physiology and acromegaly led to studies on the role of dopamine agonists and established their place in the treatment of acromegaly. Parallel work established the principals of human PRL physiology and laid the groundwork for the use of bromocriptine in the management of hyperprolactinemia. In this latter area Dr. Thorner was the major proponent of medical therapy of PRL-secreting pitutiary tumors, He established the efficacy of bromocriptine in restoring pituitary-gonadal function and in the long-term management of prolactinomas. Of real import was the demonstration that pituitary tumor size rapidly regressed during bromocriptine treatment, which allayed doubts that medical therapy did not address the mass effects of PRL-secreting pituitary tumors. In 1977, Dr. Thorner accepted a position as Associate Professor of Medicine at the University of Virginia and together with Drs. MacLeod, Rogol, and Evans among others, began elucidating the neuroregulation of PRL secretion. He also pursued basic investigation of the mechanisms of hypothalamic hormone action on GH, ACTH, and gonadotropin secretionfrom isolated pituitary cells, This active involvement in both laboratory and clinical research allowed problems in clinical endocrinology to be directly investigated at the bench. A superb example is seen in events which led to the isolation and structural identification of GH-releasing hormone (GHRH). A patient with acromegaly was referred for pituitary surgery which failed to restore normal GH
secretion. Joint work with Dr. Kalman Kovacs (University of Toronto) indicated that the pituitary showed somatotroph hyperplasia, suggesting the presence of a GH-stimulating substance. Logical thinking led to investigations which revealed the presenceof a pancreatic tumor, removal of which restored plasma GH and somatomedin to normal. Realizing the opportunity presented by these events, Dr. Thorner provided the tumor to scientists at the Salk Institute which led to characterization of GHRH. This concluded a long search for GHRH which had been hampered by the coexistence of somatostatin in hypothalamic extracts. It also typifies Dr. Thorner’s innovative approach to endocrinology and refusal to accept superficial explanations for failure of therapy-the true hallmark of a physician-scientist. Subsequent synthesis of GHRH allowed studies of the mechanismsof GHRH action, and development of in vitro systemsfurthered our knowledge of the roles of the GHRH, somatostatin, and somatomedinsin the physiological control of GH secretion. In parallel with these basic studies, Dr. Thorner played a lead role in establishing the application of GHRH to the treatment of GH deficiency. He first demonstrated the efficacy of GHRH in stimulating GH, somatomedin-C, and subsequent growth in GH-deficient patients. This work established effective therapeutic protocols but also provided important insight into the roles of somatostatin and GHRH in regulating GH secretion. Recognition of the intermittent nature of GH secretion during continuous infusion of GHRH led to the proposal that intermittent hypothalamic somatostatin secretion occurs in humans, thus establishing the dual roles of GHRH and somatostatin in regulating normal pulsatile GH secretion. Dr. Thorner’s accomplishments have been recognized by many invitations to present his work at national and inter-
Downloaded from https://academic.oup.com/endo/article-abstract/131/2/993/2496343 by East Carolina University user on 16 January 2019
for the Edwin B. Astwood Endocrine Society to Michael
Citation for the Fred Conrad Koch Award Endocrine Society to Melvin M. Grumbach Selna L. Kaplan
of The and
The Endocrine Society is pleased to bestow its most prestigious honor, the Fred Conrad Koch award, on that dynamic duo of pediatric endocrinology, Melvin M. Grumbach and Selna L. Kaplan. Mel and Selna have collaborated for 35 yr, influencing much of our understanding of pituitary physiology, growth, puberty and neuroendocrinology, and virtually every aspect of pediatric endocrinology. Mel got off to a quick start, with an M.D. from Columbia University in 1948 at the tender age of 22, and he completed his fellowship with the legendary Lawson Wilkins in 1955.
993
Like many of us, Mel was always interested in sex. While with Wilkins he began his studies of sex chromatin and its various disorders in hermaphroditism and of the disorders of adrenal steroid synthesiscausing pseudohermaphroditism. Upon moving back to Columbia University to head the newly formed division of Pediatric Endocrinology, Mel continued his landmark studies of sex chromatin, showing that all human X chromosomesin excessof one replicated late and proving that late replication caused heterochromatinization and formation of sex chromatin (the Barr body). He advanced the fixed differentiation hypothesis of X chromosomebehavior independently of Mary Lyon (but somehow the term “Grumbachianization” of sex chromatin never caught on). He showed that the second X chromosome was not completely inactive, and that geneson the second X chromosome were necessaryfor normal ovarian development. He and his colleaguescorrelated karyotypes and phenotypes in sex chromosomeabnormalities, leading to his independent discovery of the discordance between phenotype and sex chromatin pattern in Turner and Klinefelter syndromes. Obviously things were going well for Mel, but his research effort made a quantum leap forward in 1958 when Selna Kaplan joined Mel as one of his first postdoctoral fellows. Selna was also a native New Yorker but had taken a longer course before returning home. Crowded with returning veterans on the GI bill, the medical schools of the late 1940s did not welcome women with open arms. Selna outfoxed them by first going to graduate school, earning her Ph.D. in Anatomy from Washington University (St. Louis) in 1953 and her M.D. from the same*institution in 1955. When Selna joined Mel’s ‘lab, two really hot fields were just beginning to make their mark in endocrinology. First, Bersonand Yalow were developing immunoassaytechnology uptown at the Bronx VA Hospital. Second, new techniques
Downloaded from https://academic.oup.com/endo/article-abstract/131/2/993/2496343 by East Carolina University user on 16 January 2019
in studies of PTH and the PTH-related peptide. His group developed models for the three-dimensional structures of the receptor-binding portions of these molecules that gave insight into how these two molecules could bind to the same receptor in spite of a significant lack of homology in important portions of the molecules. Aspects of the models were confirmed by spectroscopic analyses. The group has used these models to design novel antagonists and agonists with potential pharmacological usefulness. More recently, Cohen and McKerrow have demonstrated further the power of structural biology methods for designing novel pharmaceuticals in their studies of an elastase which the water-borne cercariae of schistosomes secrete to bore through the foot pad of the host and enter the lymphatic system and ultimately the liver. They constructed a threedimensional model of the elastase and designed mechanismbased inhibitors that block both elastase activity and infectivity of the organism in ho. Fred has been a member of The Endocrine Society since 1989. Additional indications of his impact are reflected by his numerous invitations to speak at major meetings such as the American Chemical Society, American Physical Society, ICN/UCLA Symposia, and the National Academy of Sciences, service on the NIH Biophysics and Biochemical Chemistry Study Section, service on the editorial boards of the Journal of Molecular Biology and Protein Engineering, and receipt of NIH grants and a program grant from the Defense Advanced Research Project Agency. He currently supervises eight postdoctoral fellows and graduate students and is widely sought after by biotechnology and pharmaceutical companies as a consultant on drug design. While developing a program in research with international impact, Fred has also developed into one of UCSF’s most sought-after teachers who is equally comfortable on the medical wards reviewing problems in endocrinology or general internal medicine, or in the basic departments. He is respected by his colleagues as an excellent clinical endocrinologist and internist and as such defies the trend of the disappearing triple threat. Fred thus represents an unusual combination of clinical endocrinologist and structural biochemist who is at the forefront of a technology that is likely to have even greater impact on endocrinology in the future. The Endocrine Society is proud to award him the Richard E. Weitzman Award.
SOCIETY
994
THE ENDOCRINE
Endo - 1992 Voll31 . No 2
largely in Endocrinology; number 26 in this series appeared in December 199 1. Beyond these and a great number of other achievements in clinical endocrinology and whole animal physiology, perhaps Mel and Selna’s greatest impact has been through the people they trained. Over 80 postdoctoral fellows and visiting scientists learned from and worked with Mel and Selna. Over 35 of these now head their own laboratories, 26 are professors, and 10 chair departments of pediatrics. Both have vigorously championed the rights of children, stringent review of clinical experimentation, and careful consideration of the social impact of medical technology. In an era of premature enthusiasm and media hype, they have been the voice of restraint in the use of biosynthetic hGH for treating short healthy non-GH deficient children. This unmatched record of achievement in endocrinology and pediatrics has not gone unnoticed. Although a detailed list of all their awards and honors would take many pages, a few highlights include the following. Both have served as president of the Lawson Wilkins Pediatric Endocrine Society, Selna has served as president of the Western Society for Pediatric Research, and Mel served as president of The Endocrine Society in 1984. They have served on NIH study sections and councils and on innumerable national advisory boards in endocrinology and pediatrics, served on about a dozen editorial boards of journals, and have been elected to dozens of national and international societies. Our society previously honored Mel with the Robert H. Williams Leadership Award in 1980 and honored Selna with the Ayerst Service Award in 1987. Mel is also a member of the Institute of Medicine of the National Academy of Sciences and received an honorary doctorate from the University of Geneva in 1991. Thus, in view of this long record of outstanding achievement in basic and clinical research, of service to science,
Downloaded from https://academic.oup.com/endo/article-abstract/131/2/993/2496343 by East Carolina University user on 16 January 2019
in protein purification, pioneered by the late C. H. Li, led to the isolation of most of the pituitary hormones in pure form. Mel and Selna quickly mastered these new technologies. They were among the first to use human GH (hGH) RIA to delineate the roles of hGH in various disorders of growth, and they were the first to show that the whole hGH molecule was needed for activity, when most thought a small core peptide sequence would suffice. They developed RIAs for other hormones, including LH, FSH, TSH, and PRL. Not content just to measure hormones, they codiscovered one of their own-human chorionic somatomammotropin (sometimes termed placental lactogen)-and described its GH-like activity and its first RIA. In 1966 Mel and Selna followed Horace Greeley’s advice and headed west. Mel had been appointed Chairman of Pediatrics at the University of California, San Francisco, and Selna took over the operation of the pediatric endocrine research laboratory. Their new environment proved even more productive than the old. Based on incisive analysis of TRH-induced changes in PRL concentrations, Mel and Selna were the first to show that the overwhelming majority of children with idiopathic hypopituitarism or isolated GH deficiency had a hypothalamic, rather than a pituitary disease. They have always been leaders in the scientific investigation of disorders of growth and the use and effects of GH, publishing dozens of widely cited papers in this field. They defined the syndromes of neonatal hypopituitarism with hypoglycemia, of septo-optic dysplasia, and of hypopituitarism as a consequence of central nervous system (CNS) irradiation When the mini-epidemic of Creutzfeld-Jacob disease in recipients of pituitary-derived GH was discovered, the pediatric endocrine community turned to Selna Kaplan for guidance. As chairman of the Growth Hormone Subcommittee and president of the Lawson Wilkins Pediatric Endocrine Society, she worked with NIH officials to gather data and inform patients and provided a perspective and a firm, logical hand in the face of exaggerated fears, claims, and counterclaims. As principal investigator of the first national trial of hGH made by recombinant DNA technology she greatly facilitated the expeditious approval of biosynthetic hGH to replace pituitary hGH. Using exquisitely sensitive RIAs for gonadotropins and sex steroids, Mel and Selna painstakingly described the hormonal changes in normal infants and in children in puberty. They described the striking rise of LH in response to GnRH that precedes clinical signs of puberty and demonstrated the increasing insensitivity of sex-steroid feedback on the hypothalamus as puberty advances. They discovered that puberty is restrained in normal children by the CNS rather than by sex steroids and showed that it was the waning of this CNS inhibition that initiates puberty. They showed that the onset of adrenarche is independent of puberty and were among the first to describe the use of GnRH agonists in the treatment of precocious puberty. Beginning in the late 1970s they initiated work with the chronically catheterized sheep fetus, a technically demanding but powerful physiological system for delineating the developmental endocrinology of the third trimester mammalian fetus. This led to their continuing series of papers, “Hormone ontogeny in the ovine fetus,” published
SOCIETY
THE ENDOCRINE
SOCIETY
995
medicine, and society, and in training the next generation of endocrinologists, The Endocrine Society bestows the 1992 Fred Conrad Koch Award on Melvin M. Grumbach and Selna L. Kaplan. Citation
Lectureship 0. Thorner
of The
The Endocrine Society has selected Michael 0. Thorner, M.B., B.S., DSc., Professor of Medicine, Chief of the Division of Endocrinology, and Director of the General Clinical Research Center at the University of Virginia, as the recipient of the 1992 Edwin B. Astwood Lectureship for Scientific Achievement. This selection recognizes his outstanding contributions to clinical and basic research in neuroendocrinol%Y* Dr. Thorner was born in Beaconsfield, west of London, UK, and received his M.B., B.S. with honors, in 1970 from the Middlesex Hospital at the University of London. Clinical training followed the English pattern with internship and residency in a wide spectrum of subspecialties at several London hospitals. A long-standing interest in endocrinology was pursued by fellowship with Michael Besserand subsequent appointment as Lecturer in Medicine at St. Bartholomew’s, one of the major endocrine training centers in the UK. During this time, Dr. Thorner developed his interest in neuroendocrinology, and he played a major role in establishing the basic physiology and clinical applications of somatostatin. This work established the clinical effects of somatostatin in the gastrointestinal tract and on GH secretion, and was the forerunner of the current use of long-acting somatostatin analogsin the treatment of acromegaly. This interest in GH physiology and acromegaly led to studies on the role of dopamine agonists and established their place in the treatment of acromegaly. Parallel work established the principals of human PRL physiology and laid the groundwork for the use of bromocriptine in the management of hyperprolactinemia. In this latter area Dr. Thorner was the major proponent of medical therapy of PRL-secreting pitutiary tumors, He established the efficacy of bromocriptine in restoring pituitary-gonadal function and in the long-term management of prolactinomas. Of real import was the demonstration that pituitary tumor size rapidly regressed during bromocriptine treatment, which allayed doubts that medical therapy did not address the mass effects of PRL-secreting pituitary tumors. In 1977, Dr. Thorner accepted a position as Associate Professor of Medicine at the University of Virginia and together with Drs. MacLeod, Rogol, and Evans among others, began elucidating the neuroregulation of PRL secretion. He also pursued basic investigation of the mechanisms of hypothalamic hormone action on GH, ACTH, and gonadotropin secretionfrom isolated pituitary cells, This active involvement in both laboratory and clinical research allowed problems in clinical endocrinology to be directly investigated at the bench. A superb example is seen in events which led to the isolation and structural identification of GH-releasing hormone (GHRH). A patient with acromegaly was referred for pituitary surgery which failed to restore normal GH
secretion. Joint work with Dr. Kalman Kovacs (University of Toronto) indicated that the pituitary showed somatotroph hyperplasia, suggesting the presence of a GH-stimulating substance. Logical thinking led to investigations which revealed the presenceof a pancreatic tumor, removal of which restored plasma GH and somatomedin to normal. Realizing the opportunity presented by these events, Dr. Thorner provided the tumor to scientists at the Salk Institute which led to characterization of GHRH. This concluded a long search for GHRH which had been hampered by the coexistence of somatostatin in hypothalamic extracts. It also typifies Dr. Thorner’s innovative approach to endocrinology and refusal to accept superficial explanations for failure of therapy-the true hallmark of a physician-scientist. Subsequent synthesis of GHRH allowed studies of the mechanismsof GHRH action, and development of in vitro systemsfurthered our knowledge of the roles of the GHRH, somatostatin, and somatomedinsin the physiological control of GH secretion. In parallel with these basic studies, Dr. Thorner played a lead role in establishing the application of GHRH to the treatment of GH deficiency. He first demonstrated the efficacy of GHRH in stimulating GH, somatomedin-C, and subsequent growth in GH-deficient patients. This work established effective therapeutic protocols but also provided important insight into the roles of somatostatin and GHRH in regulating GH secretion. Recognition of the intermittent nature of GH secretion during continuous infusion of GHRH led to the proposal that intermittent hypothalamic somatostatin secretion occurs in humans, thus establishing the dual roles of GHRH and somatostatin in regulating normal pulsatile GH secretion. Dr. Thorner’s accomplishments have been recognized by many invitations to present his work at national and inter-
Downloaded from https://academic.oup.com/endo/article-abstract/131/2/993/2496343 by East Carolina University user on 16 January 2019
for the Edwin B. Astwood Endocrine Society to Michael
