Identification of a new G-protein-linked receptor for growth hormone secretagogues
Sheng-Shung Pong,Lee-Yuh Chaung,Dennis C. Dean,Ravi P. Nargund,Arthur A. Patchett,Roy G. Smith +5 more
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TLDR
A specific high affinity binding site in porcine and rat anterior pituitary membranes that mediates the activity of these secretagogues has now been identified and is tightly correlated with GH-secretory activity.Abstract:
The potential application of small molecules in GH therapy has recently become a topic of increasing interest The spiroindoline MK-0677, the benzolactam L-692,429, and the peptides, GHRP-6 and hexarelin, have been shown to possess potent and selective GH-secretory activity in several species including human Moreover, these synthetic GH secretagogues act on a signal transduction pathway distinct from that of GHRH A specific high affinity binding site in porcine and rat anterior pituitary membranes that mediates the activity of these secretagogues has now been identified The binding affinity of these structurally diverse secretagogues is tightly correlated with GH-secretory activity The binding is Mg(2+)-dependent, is inhibited by GTP-gamma-S, and is not displaced by GHRH and somatostatin The receptor is distinct from that for GHRH and has the properties of a new G-protein-coupled receptor It is speculated that these GH secretagogues mimic an unidentified natural hormone that regulates GH secretion iread more
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Journal ArticleDOI
Ghrelin: Structure and Function
Masayasu Kojima,Kenji Kangawa +1 more
TL;DR: The discovery of ghrelin indicates that the release of GH from the pituitary might be regulated not only by hypothalamic GH-releasing hormone, but also by gh Relin derived from the stomach, which plays important roles for maintaining GH release and energy homeostasis in vertebrates.
Journal ArticleDOI
A Receptor in Pituitary and Hypothalamus That Functions in Growth Hormone Release
Andrew D. Howard,Scott D. Feighner,Doris F. Cully,Joseph P. Arena,Paul A. Liberator,Charles Rosenblum,Michel J. Hamelin,Donna L. Hreniuk,Oksana C. Palyha,Jennifer W. Anderson,Philip S. Paress,Carmen Diaz,Michael Chou,Ken K. Liu,Karen K. McKee,Sheng-Shung Pong,Lee-Yuh Chaung,Alex Elbrecht,Mike Dashkevicz,Robert P. Heavens,Michael Rigby,Dalip J. S. Sirinathsinghji,Dennis C. Dean,David G. Melillo,Arthur A. Patchett,Ravi P. Nargund,Patrick R. Griffin,Julie A. DeMartino,Sunil Gupta,James M. Schaeffer,Roy G. Smith,Lex H.T. Van der Ploeg +31 more
TL;DR: A heterotrimeric GTP-binding protein (G protein)-coupled receptor (GPC-R) of the pituitary and arcuate ventro-medial and infundibular hypothalamus of swine and humans was cloned and was shown to be the target of the GHSs.
Journal ArticleDOI
Biological, physiological, pathophysiological, and pharmacological aspects of ghrelin.
TL;DR: Ghrelin is considered a gastrointestinal peptide contributing to the regulation of diverse functions of the gut-brain axis and there is indeed a possibility that ghrelin analogs, acting as either agonists or antagonists, might have clinical impact.
Journal ArticleDOI
Pathophysiology of the neuroregulation of growth hormone secretion in experimental animals and the human
TL;DR: The pathophysiology of the GHRH somatostatin-GH-IGF-I feedback axis is reviewed and it is proposed that this system is best viewed as a multivalent feedback network that is exquisitely sensitive to an array of neuroregulators and environmental stressors and genetic restraints.
Journal ArticleDOI
Distribution of mRNA encoding the growth hormone secretagogue receptor in brain and peripheral tissues.
Xiao-Ming Guan,Hong Yu,Oksana C. Palyha,Karen K. McKee,Scott D. Feighner,Dalip J. S. Sirinathsinghji,Roy G. Smith,Lex H.T. Van der Ploeg,Andrew D. Howard +8 more
TL;DR: The demonstration of hypothalamic and pituitary localization of the GHS-R is consistent with its role in regulating growth hormone release and the expression of the receptor in other central and peripheral regions may implicate its involvement in additional as yet undefined physiological functions.
References
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Journal ArticleDOI
Characterization of a growth hormone-releasing factor from a human pancreatic islet tumour.
TL;DR: A synthetic replicate of this peptide, termed human pancreatic tumour GRF [hpGRF(1–40)]-OH, co-elutes on HPLC with the native peptide and is highly potent in stimulating GH secretion in vitro and in vivo.
Journal ArticleDOI
A nonpeptidyl growth hormone secretagogue
Roy G. Smith,Kang Cheng,William R. Schoen,Sheng-Shung Pong,Gerard J. Hickey,Tom Jacks,B. Butler,Wanda W.-S. Chan,L.-Y. Chaung,F Judith +9 more
TL;DR: The mechanism of action of L-692,429 and studies with peptidyl and nonpeptidyl antagonists suggest that this molecule is a mimic of the growth hormone-releasing hexapeptide His-D-Trp-Ala-Tr phe-Phe-Lys-NH2 (GHRP-6).
Journal ArticleDOI
The synergistic effects of His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 on growth hormone (GH)-releasing factor-stimulated GH release and intracellular adenosine 3',5'-monophosphate accumulation in rat primary pituitary cell culture.
TL;DR: Results from this study indicate that GHRP-6 and GRF stimulated GH release from somatotrophs via different receptors and through discrete mechanisms.
Journal ArticleDOI
Stimulation of Adenosine 3′,5′-Monophosphate Production by Growth Hormone-Releasing Factor and Its Inhibition by Somatostatin in Anterior Pituitary Cells in Vitro
Louise M. Bilezikjian,Wylie Vale +1 more
TL;DR: CAMP may play a role as an intracellular mediator of GRF action in somatotrophs and that Ca2+ is required for the release process and a requirement for Ca2- is indicated by the inhibitory effects of CoCl2 and CdCl2 on both basal and hpGRF-stimulated GH release.
Journal ArticleDOI
Design, Synthesis, and Biological Activity of Peptides which Release Growth Hormone in Vitro
TL;DR: From the structure-activity data, a mechanism for binding at the receptors is formulated, and a comparison is made between the structural relationships of the GH-releasing peptide analogs and the GH inhibitor, somatostatin.
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