Richard F. Walker – 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!

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!

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.

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.

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.