Growth Hormone Secretagogues

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.

Contenu

I. Overview: Historical Perspective.- Growth Hormone Releasing Factor: A Brief History of Its Time.- 2. Xenobiotic Growth Hormone Secretagogues: Growth Hormone Releasing Peptides.- II. Chemistry of Growth Hormone Secretagogues.- 3. Synthetic Analogues of Growth Hormone Releasing Factor (GHRF) with Improved Pharmaceutical Properties.- 4. Structure, Function, and Regulation of the Pituitary Receptor for Growth Hormone Releasing Hormone.- 5. Computer-Assisted Modeling of Xenobiotic Growth Hormone Secretagogues.- 6. Growth Hormone Releasing Peptides.- 7. Nonpeptidyl Growth Hormone Secretagogues.- 8. A Weak Substance P Antagonist Inhibits L-692,585-Stimulated GH Release in Swine.- 9. Growth Hormone Releasing Hormone Receptor in Human Breast Cancer Cell Line MCF-7.- III. Cellular and Molecular Properties of Growth Hormone Secretagogues.- 10. Cellular Physiology of Growth Hormone Releasing Hormone.- 11. Mechanism of Action of GHRP-6 and Nonpeptidyl Growth Hormone Secretagogues.- 12. Metabolic Regulation of Growth Hormone Secretagogue Gene Expression.- IV. Physiology of Growth Hormone Secretagogues.- 13. The Role of Growth Hormone Releasing Hormone (GHRH) and Growth Hormone (GH) in the Onset of Puberty and During Glucocorticoid-Altered Growth.- 14. Clinical Studies with Growth Hormone Releasing Hormone.- 15. Central and Peripheral Effects of Peptide and Nonpeptide GH Secretagogues on GH Release In Vivo.- 16. Evidence for a Central Site and Mechanism of Action of Growth Hormone Releasing Peptide (GHRP-6).- 17. Animal Models for Evaluating Xenobiotic Growth Hormone Secretagogue Activity.- 18. A Diagnostic Test Employing Growth Hormone Secretagogues for Evaluating Pituitary Function in the Elderly.- V. Target Tissues and Applications for Growth Hormone Secretagogues.- 19. Transdifferentiation of Growth Hormone and Prolactin Secreting Cells.- 20. Growth Hormone Releasing Hormone: Behavioral Evidence for Direct Central Actions.- 21. Growth Hormone (GH) Releasing Hormone- and Thyrotropin Releasing Hormone-Induced GH Release in the Acute Phase of Trauma.- 22. Effects of Hexarelin on Growth Hormone Secretion in Short Normal Children, in Obese Children, and in Subjects with Growth Hormone Deficiency.- 23. Lymphocytes and Hypothalamic Peptides.- 24. Growth Hormone Releasing Peptide-Hexarelin-in Children: Biochemical and Growth Promoting Effects.- 25. Growth Hormone Secretagogues in Disease States Associated with Altered Growth Hormone Secretion.- 26. Growth Hormone Releasing Hormone (GHRH) Effects in Healthy Aging Men.- 27. Aging and Growth Hormone Releasing Peptides.- 28. Growth Hormone Relationships to Immune Function in Humans.- Author Index.