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Pharmacology of Growth Hormone-Releasing Hormone and Its Peptide Analogs

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Human Growth Hormone

Part of the book series: Contemporary Endocrinology ((COE,volume 19))

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Abstract

When the isolation (from human pancreatic growth hormone [GH]-secreting tumors) and structures of several forms of growth hormone-releasing hormone (GHRH) were first reported (1,2), much surprise was generated by the size of the peptide since all previously sequenced hypothalamic hormones were made up of relatively short amino-acid sequences. Also surprising at the time was the high degree of amino-acid sequence homology between GHRH and members of the quite extensive vasoactive intestinal polypeptide (VIP)/glucagon family of peptides (Fig. 1) all of which were of gastrointestinal or pancreatic origin. There is clearly a common evolutionary pathway, presumably owing to gene duplication, which has resulted in two major branches of this family: GHRH/PACAP, VIP/PHI, and secretin on one hand and glucagon/glucagon-like polypeptide (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) on the other and these aspects have been reviewed recently (3). As with other known hypothalamic hormones, with the exception of somatostatin, GHRH is highly specific having demonstrable potent biological activity on GH release from the pituitary. However, there are indications that GHRH might also play a peripheral role, for instance in fetal/placental development, reproduction, and immune function (3,4). Indeed, GHRH immunoreactivity has been found not only in the hypothalamus and pituitary but also in pancreas, kidney, duodenum, lung, testis, ovary, adrenal, heart, and brain (5,6). Although the biological responses, if any, of GHRH at these tissues are far from being fully characterized, the peptide does stimulate pancreatic exocrine secretion in vitro and in vivo (7,8) and weakly interacts with receptors for other GI peptides, particularly VIP (9,10). There is also evidence of GHRH has effects on secretion of other peptides from several cell lines, for instance, stimulation of neurotensin and calcitonin from rat C cells (11). These additional interactions and activities have to be kept in mind during the design of highly potent peptide analogs of GHRH in case unwanted side effects are inadvertently enhanced.

Amino-acid sequences of peptides in the same family as GHRH. Vertical lines indicate where sequence shortening can be effected with little loss of potency. Basic residues are emphasized in order to highlight there different spacing from peptide to peptide-this may influence their receptor specificity (see text).

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  1. David H. Coy PhD
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Editors and Affiliations

  1. Huffington Center on Aging and Department of Cell Biology, Baylor College of Medicine, Houston, TX, USA

    Roy G. Smith PhD

  2. Department of Medicine, University of Virginia Health Sciences Center, Charlottesville, VA, USA

    Michael O. Thorner MD

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Coy, D.H. (2000). Pharmacology of Growth Hormone-Releasing Hormone and Its Peptide Analogs. In: Smith, R.G., Thorner, M.O. (eds) Human Growth Hormone. Contemporary Endocrinology, vol 19. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-015-5_6

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  • DOI: https://doi.org/10.1007/978-1-59259-015-5_6

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-4684-9610-9

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