Barry B. Bercu – författare

Recognizing the urgent need for an up-to-date review of new and innovative research on growth hormone (GH) secretagogues, this exclusive work furnishes the state of the art on the mechanisms of action, design, synthesis, evaluation, and clinical applications of GH secretagogues, including orally active and xenobiotic GH-releasing compounds. Beginning with a thorough historical perspective on the discovery and evolution of GH-releasing peptides (GHRPs) as therapeutic agents, Growth Hormone Secretagogues in Clinical Practiceanalyzes structural requirements for GH secretagogue efficacy demonstrates the use of mathematical models to predict differential values of individual stimuli for GH secretion from the pituitary reports on the development of a simple screening system based on polyclonal antibodies discusses laboratory synthesis of agonistic analogs intended for human and veterinary use proposes applications in managing conditions such as Turner's syndrome, acromegaly, diabetic retinopathy, glomerulosclerosis, tumors, and cancer provides physiological evidence for the effects of GHRP on behavior with a series of trials involving voluntary and forced exercise describes a new diagnostic test for evaluating pituitary function in slowly growing children and aging adults explores the interactions of GH secretagogues with other hormones and endogenous substances from sex steroids to interferons and much more!

"Therapeutic Outcome of Endocrine Disorders: Efficacy, Innovation and Quality of Life" presents the proceedings of an international symposium held from November 13-16, 1997 in Palm Beach Gardens, Florida. The proceedings discuss scientific and clinical studies related to the treatment of endocrine disorders, including growth hormone deficiency, Turner Syndrome, constitutional delay of growth, treatment of diabetes, congenital adrenal hyperplasia, and congenital hypothyroidism.

Recognizing the urgent need for an up-to-date review of new and innovative research on growth hormone (GH) secretagogues, this exclusive work furnishes the state of the art on the mechanisms of action, design, synthesis, evaluation, and clinical applications of GH secretagogues, including orally active and xenobiotic GH-releasing compounds. Beginning with a thorough historical perspective on the discovery and evolution of GH-releasing peptides (GHRPs) as therapeutic agents, Growth Hormone Secretagogues in Clinical Practiceanalyzes structural requirements for GH secretagogue efficacy demonstrates the use of mathematical models to predict differential values of individual stimuli for GH secretion from the pituitary reports on the development of a simple screening system based on polyclonal antibodies discusses laboratory synthesis of agonistic analogs intended for human and veterinary use proposes applications in managing conditions such as Turner's syndrome, acromegaly, diabetic retinopathy, glomerulosclerosis, tumors, and cancer provides physiological evidence for the effects of GHRP on behavior with a series of trials involving voluntary and forced exercise describes a new diagnostic test for evaluating pituitary function in slowly growing children and aging adults explores the interactions of GH secretagogues with other hormones and endogenous substances from sex steroids to interferons and much more!

Changes in the allocation of healthcare resources have raised issues related to the efficacy and outcomes of medical therapy and how such factors may be measured. The questions associated with the quality of life and functional capability of patients with chronic health conditions have been of special interest. Endocrine disorders have the potential for disrupting the general health and well-being of affected individuals and their families; thus they warrant serious attention. This symposium was convened in November 1997 at Palm Beach Gardens, Florida, to bring together medical, behavioral, and social scientists. The meeting fostered the presentation and discussion of the most current clinical research on the effects of various therapies on a wide range of endocrine disorders from diabetes to adrenal insufficiency and growth hormone deficiency. The participants, all noted national and international experts in their fields, focused their attention on both the biomedical value and effectiveness of treatment, as well as on the impact such treatments have on psychological states such as mood and cognition. Many presentations specifically emphasized the quality of life (QOL) indicators that now regu­ larly appear in many research protocols and reports. The pioneering work of two clinical researchers was a major highlight of the meeting and an Award of Recognition was presented to Robert Blizzard, M. D. , and John Money, Ph. D. , for their innovative and insightful work in pediatric endocrinology and psychosexual development.

The traditional concept of a neuroendocrine mechanism for regulation of growth hormone (GH) secretion is based in large part on the work of Roger Guillemin. The work of Dr. Guillemin, who was awarded the 1977 Nobel Prize in Physiology and Medicine, supported the view that quantita­ tive change in GH secretion was the net result of pituitary stimulation and inhibition by the hypothalamic neurohormones, GH releasing hormone (GHRH), and somatostatin (somatotropin release inhibiting factor; SRIF), respectively. During the 1970s, another endocrine research pioneer, Dr. Cyril Bowers, discovered that structural modification of enkephalin re­ sulted in a family of peptides with GH releasing properties. These com­ pounds, simply called GH releasing peptide (GHRP), were originally thought to mimic GHRH. However, upon subsequent investigation they were found to supplement the activity of the natural hormone through a different mechanism. Nearly two decades after their discovery, the differ­ ences between GHRP and GHRH have been described by many different laboratories throughout the world. The complementary GH secretagogues have different binding sites, second messengers, and effects on gene expres­ sion. Based on these differences, it has been suggested that expansion of the original two hormone mechanisms for GH regulation to include a third molecule may be appropriate, even though the naturally occurring ana­ logue of GHRP has not yet been identified. Despite our lack of knowledge concerning the natural product mimicked by GHRP, clinical development of the new family of GH secretagogues for diagnostic and therapeutic purposes has begun in earnest.

ALLEN W. ROOT On November 11 and 12, 1988, a "Festschrift" was held to honor "our Chief;'' Lewis A. Barness. Who is our Chief, and why was such an occasion held? I will not attempt to describe him in terms of his scientific and scholarly accomplish­ ments, which have spanned more than four decades. Rather, I will describe the characteristics of an individual whose concern for humanity has made him the quintessential role model for countless students, residents, and graduate pediatri­ cians around the world. The Chief''s concern is manifested by his love for chil­ dren and his tireless efforts on their behalf, as well as his genuine affection for his colleagues, all of whom are also his friends. During the 2-day celebration, many of these friends had an opportunity to make comments which I believe capture portions of the essence of this remark­ able human being: Many of us are better persons because of our association with the "Chief . . . :'' Many of us have chosen pediatrics as a career as an unspoken act of tribute to him . . . . We love you and we thank you for making the world a better place to spend some time. (F. Oski) Lew fulfilled all our dreams . . . We all wish we could have done half so well. (R. Klein) [Your] ever-present evidence of concern for your fellow man . . . it is the quality of car­ ing. (T.

Changes in the allocation of healthcare resources have raised issues related to the efficacy and outcomes of medical therapy and how such factors may be measured. The questions associated with the quality of life and functional capability of patients with chronic health conditions have been of special interest. Endocrine disorders have the potential for disrupting the general health and well-being of affected individuals and their families; thus they warrant serious attention. This symposium was convened in November 1997 at Palm Beach Gardens, Florida, to bring together medical, behavioral, and social scientists. The meeting fostered the presentation and discussion of the most current clinical research on the effects of various therapies on a wide range of endocrine disorders from diabetes to adrenal insufficiency and growth hormone deficiency. The participants, all noted national and international experts in their fields, focused their attention on both the biomedical value and effectiveness of treatment, as well as on the impact such treatments have on psychological states such as mood and cognition. Many presentations specifically emphasized the quality of life (QOL) indicators that now regu­ larly appear in many research protocols and reports. The pioneering work of two clinical researchers was a major highlight of the meeting and an Award of Recognition was presented to Robert Blizzard, M. D. , and John Money, Ph. D. , for their innovative and insightful work in pediatric endocrinology and psychosexual development.

The traditional concept of a neuroendocrine mechanism for regulation of growth hormone (GH) secretion is based in large part on the work of Roger Guillemin. The work of Dr. Guillemin, who was awarded the 1977 Nobel Prize in Physiology and Medicine, supported the view that quantita­ tive change in GH secretion was the net result of pituitary stimulation and inhibition by the hypothalamic neurohormones, GH releasing hormone (GHRH), and somatostatin (somatotropin release inhibiting factor; SRIF), respectively. During the 1970s, another endocrine research pioneer, Dr. Cyril Bowers, discovered that structural modification of enkephalin re­ sulted in a family of peptides with GH releasing properties. These com­ pounds, simply called GH releasing peptide (GHRP), were originally thought to mimic GHRH. However, upon subsequent investigation they were found to supplement the activity of the natural hormone through a different mechanism. Nearly two decades after their discovery, the differ­ ences between GHRP and GHRH have been described by many different laboratories throughout the world. The complementary GH secretagogues have different binding sites, second messengers, and effects on gene expres­ sion. Based on these differences, it has been suggested that expansion of the original two hormone mechanisms for GH regulation to include a third molecule may be appropriate, even though the naturally occurring ana­ logue of GHRP has not yet been identified. Despite our lack of knowledge concerning the natural product mimicked by GHRP, clinical development of the new family of GH secretagogues for diagnostic and therapeutic purposes has begun in earnest.

ALLEN W. ROOT On November 11 and 12, 1988, a "Festschrift" was held to honor "our Chief;' Lewis A. Barness. Who is our Chief, and why was such an occasion held? I will not attempt to describe him in terms of his scientific and scholarly accomplish­ ments, which have spanned more than four decades. Rather, I will describe the characteristics of an individual whose concern for humanity has made him the quintessential role model for countless students, residents, and graduate pediatri­ cians around the world. The Chief's concern is manifested by his love for chil­ dren and his tireless efforts on their behalf, as well as his genuine affection for his colleagues, all of whom are also his friends. During the 2-day celebration, many of these friends had an opportunity to make comments which I believe capture portions of the essence of this remark­ able human being: Many of us are better persons because of our association with the "Chief . . . :' Many of us have chosen pediatrics as a career as an unspoken act of tribute to him . . . . We love you and we thank you for making the world a better place to spend some time. (F. Oski) Lew fulfilled all our dreams . . . We all wish we could have done half so well. (R. Klein) [Your] ever-present evidence of concern for your fellow man . . . it is the quality of car­ ing. (T.

This book is a compendium of proceedings from the Symposium on Growth Hormone II: Basic and Clinical Aspects. The intent of the sym­ posium was to review current aspects of the rapidly expanding science of growth hormone (GH) neuroendocrinology, especially those develop­ ments that occurred since our last meeting in 1985. The meeting was timely since there have been many new and exciting developments in basic research on the GH axis, and several new clinical applications for GH other than growth have been identified. For example, significant strides have been made into use of the bioengineered hormone as an anabolic in debilitated states and as an immunorestorative agent. Both these areas have received most attention as they relate to geriatric popu­ lations. Furthermore, recent focus on a novel family of GH secretagogues that complement the action of GHRH has shown that in animal models, these compounds have the potential to restore GH secretion in deficient or insufficient states, including growth retardation, obesity, and aging. Accordingly, these xenobiotics may have significant potential as drug products to stimulate physiological GH secretion and, thus, resist or reverse some of the maladaptive changes in form and function resulting from GH insufficiency. The importance of these agents as drug candidates is underscored by the diversity of molecules that have been studied by various pharmaceutical companies and the recent discovery that non­ peptide analogs with high oral bioavailability can be synthesized.

This book is a compendium of proceedings from the Symposium on Growth Hormone II: Basic and Clinical Aspects. The intent of the sym­ posium was to review current aspects of the rapidly expanding science of growth hormone (GH) neuroendocrinology, especially those develop­ ments that occurred since our last meeting in 1985. The meeting was timely since there have been many new and exciting developments in basic research on the GH axis, and several new clinical applications for GH other than growth have been identified. For example, significant strides have been made into use of the bioengineered hormone as an anabolic in debilitated states and as an immunorestorative agent. Both these areas have received most attention as they relate to geriatric popu­ lations. Furthermore, recent focus on a novel family of GH secretagogues that complement the action of GHRH has shown that in animal models, these compounds have the potential to restore GH secretion in deficient or insufficient states, including growth retardation, obesity, and aging. Accordingly, these xenobiotics may have significant potential as drug products to stimulate physiological GH secretion and, thus, resist or reverse some of the maladaptive changes in form and function resulting from GH insufficiency. The importance of these agents as drug candidates is underscored by the diversity of molecules that have been studied by various pharmaceutical companies and the recent discovery that non­ peptide analogs with high oral bioavailability can be synthesized.

Perinatal problems in thyroid gland physiology are common but complicated and present a diagnostic dilemma for the primary clinician. In December 1990, an international group of basic and clinical investigators gathered in Longboat Key, Florida to address these issues. The participants included internists, obstetricians, pedia­ tricians, neurologists, pathologists and basic scientists in cellular metabolism, endocrine physiology, and molecular biology. The presentations contained within this book bring together their most current and vital research related to the field of perinatal thyroidology. This book is based on the dynamic and fruitful exchange of the participants at the symposium. We are indebted to these individuals whose valuable insights and efforts are contained within this text. Barry B. Bercu Dorothy I. Shulman vii CONTENTS Session I Mechanism of Thyroid Hormone Action 1 Leslie J. DeGroot Thyroid System Ontogeny in the Sheep: A Model for Precocial Mammalian Species • . . • • 11 Delbert A. Fisher Pathologic Studies of Fetal Thyroid 27 Development • • • • • • • Douglas R. Shanklin Thyroid Hormone Control of Brain and Motor Development: Molecular, Neuroanatomical, 47 and Behavioral Studies • • • • • • • S. A. Stein, P. M. Adams, D. R. Shanklin, G. A. Mihailoff, and M. B. Palnitkar The Thyroidectomized Pregnant Rat: An Animal Model to Study Fetal Effects of Maternal Hypothyroidism 107 Susan P. Porterfield and Chester E.

Perinatal problems in thyroid gland physiology are common but complicated and present a diagnostic dilemma for the primary clinician. In December 1990, an international group of basic and clinical investigators gathered in Longboat Key, Florida to address these issues. The participants included internists, obstetricians, pedia­ tricians, neurologists, pathologists and basic scientists in cellular metabolism, endocrine physiology, and molecular biology. The presentations contained within this book bring together their most current and vital research related to the field of perinatal thyroidology. This book is based on the dynamic and fruitful exchange of the participants at the symposium. We are indebted to these individuals whose valuable insights and efforts are contained within this text. Barry B. Bercu Dorothy I. Shulman vii CONTENTS Session I Mechanism of Thyroid Hormone Action 1 Leslie J. DeGroot Thyroid System Ontogeny in the Sheep: A Model for Precocial Mammalian Species • . . • • 11 Delbert A. Fisher Pathologic Studies of Fetal Thyroid 27 Development • • • • • • • Douglas R. Shanklin Thyroid Hormone Control of Brain and Motor Development: Molecular, Neuroanatomical, 47 and Behavioral Studies • • • • • • • S. A. Stein, P. M. Adams, D. R. Shanklin, G. A. Mihailoff, and M. B. Palnitkar The Thyroidectomized Pregnant Rat: An Animal Model to Study Fetal Effects of Maternal Hypothyroidism 107 Susan P. Porterfield and Chester E.