help button home button Endocrine Society JCEM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text (PDF)
Right arrow Submit a related Letter to the Editor
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Popovic, V.
Right arrow Articles by Casanueva, F. F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Popovic, V.
Right arrow Articles by Casanueva, F. F.

Journal of Clinical Endocrinology & Metabolism, Vol 80, 942-947, Copyright © 1995 by Endocrine Society

ARTICLES

Blocked growth hormone-releasing peptide (GHRP-6)-induced GH secretion and absence of the synergic action of GHRP-6 plus GH-releasing hormone in patients with hypothalamopituitary disconnection: evidence that GHRP- 6 main action is exerted at the hypothalamic level

V Popovic, S Damjanovic, D Micic, M Djurovic, C Dieguez and FF Casanueva
Institute of Endocrinology, University Clinical Center, Belgrade, Yugoslavia.

GH-releasing peptide (GHRP-6; His-D Trp-Ala-Trp-D Phe-Lys-NH2) is a synthetic compound that releases GH in a specific and dose-related manner through mechanisms and a point of action that are mostly unknown but different from those of GHRH. In man, GHRP-6 is more efficacious than GHRH, and a striking synergistic action on GH release is observed when GHRP-6 and GHRH are administered simultaneously. Based on such a synergistic action, it has been hypothesized that GHRP-6 acts through a double mechanism by actions exerted both at the pituitary and hypothalamic levels. The aim of the present study was 2-fold: 1) to further characterize the mechanism of action and synergistic effects of GHRP-6; and 2) to study its action in patients with hypothalamopituitary disconnection. Twelve patients with different neuroendocrine pathologies leading to a state of hypothalamopituitary disconnection (functional stalk section) and 11 age- and sex-matched normal controls were studied. Each subject underwent 3 tests on separate occasions, being challenged with GHRH (100 micrograms, i.v.), GHRP-6 (90 micrograms, i.v.), or GHRH plus GHRP-6. GH was analyzed as the area under the curve (mean +/- SE, micrograms per L/120 min). In normal subjects GH secretion was 483.7 +/- 99.2 after GHRH, 1434.8 +/- 393.0 after GHRP-6, and 3771.5 +/- 399.6 after GHRH plus GHRP-6; the level of GH secreted after GHRH plus GHRP-6 treatment was significantly (P < 0.05) higher than after the arithmetic sum of GH levels after both compounds administered separately. In the group of patients with hypothalamopituitary disconnection, the level of GH secreted after GHRH was similar to that in controls (423.4 +/- 62.8); however, a complete blockade was observed after GHRP-6 (97.3 +/- 7.9), significantly (P < 0.05) lower than after GHRH as well as lower than the GHRP-6-induced GH release in control subjects (P < 0.01). After GHRH plus GHRP-6, the patients with hypothalamopituitary disconnection showed severely reduced secretion (745.3 +/- 67.6; P < 0.01 vs. controls), a value that was not significantly different from the arithmetic addition of levels produced by both compounds administered separately.(ABSTRACT TRUNCATED AT 400 WORDS)


This article has been cited by other articles:


Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
M. G.-S. Frutos, L. Cacicedo, C. Fernandez, D. Vicent, B. Velasco, H. Zapatero, and F. Sanchez-Franco
Insights into a role of GH secretagogues in reversing the age-related decline in the GH/IGF-I axis
Am J Physiol Endocrinol Metab, November 1, 2007; 293(5): E1140 - E1152.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
R. D. Kineman and R. M. Luque
Evidence that Ghrelin Is as Potent as Growth Hormone (GH)-Releasing Hormone (GHRH) in Releasing GH from Primary Pituitary Cell Cultures of a Nonhuman Primate (Papio anubis), Acting through Intracellular Signaling Pathways Distinct from GHRH
Endocrinology, September 1, 2007; 148(9): 4440 - 4449.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
J. D. Veldhuis, M. Cosma, D. Erickson, R. Paulo, K. Mielke, L. S. Farhy, and C. Y. Bowers
Tripartite Control of Growth Hormone Secretion in Women during Controlled Estradiol Repletion
J. Clin. Endocrinol. Metab., June 1, 2007; 92(6): 2336 - 2345.
[Abstract] [Full Text] [PDF]

Home page
 Eur J EndocrinolHome page
M. Maghnie, M. C. Pennati, E. Civardi, N. Di Iorgi, G. Aimaretti, M. L. Foschini, G. Corneli, C. Tinelli, E. Ghigo, R. Lorini, et al.
GH response to ghrelin in subjects with congenital GH deficiency: evidence that ghrelin action requires hypothalamic-pituitary connections
Eur. J. Endocrinol., April 1, 2007; 156(4): 449 - 454.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
L. S. Farhy, C. Y. Bowers, and J. D. Veldhuis
Model-projected mechanistic bases for sex differences in growth hormone regulation in humans
Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2007; 292(4): R1577 - R1593.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
L. S. Farhy and J. D. Veldhuis
Deterministic construct of amplifying actions of ghrelin on pulsatile growth hormone secretion
Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2005; 288(6): R1649 - R1663.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
N. Wettschureck, A. Moers, B. Wallenwein, A. F. Parlow, C. Maser-Gluth, and S. Offermanns
Loss of Gq/11 Family G Proteins in the Nervous System Causes Pituitary Somatotroph Hypoplasia and Dwarfism in Mice
Mol. Cell. Biol., March 1, 2005; 25(5): 1942 - 1948.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
J. D. Veldhuis, J. T. Patrie, K. T. Brill, J. Y. Weltman, E. E. Mueller, C. Y. Bowers, and A. Weltman
Contributions of Gender and Systemic Estradiol and Testosterone Concentrations to Maximal Secretagogue Drive of Burst-Like Growth Hormone Secretion in Healthy Middle-Aged and Older Adults
J. Clin. Endocrinol. Metab., December 1, 2004; 89(12): 6291 - 6296.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
B. Bodosi, J. Gardi, I. Hajdu, E. Szentirmai, F. Obal Jr., and J. M. Krueger
Rhythms of ghrelin, leptin, and sleep in rats: effects of the normal diurnal cycle, restricted feeding, and sleep deprivation
Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2004; 287(5): R1071 - R1079.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
A. Iranmanesh, C. Y. Bowers, and J. D. Veldhuis
Activation of Somatostatin-Receptor Subtype-2/-5 Suppresses the Mass, Frequency, and Irregularity of Growth Hormone (GH)-Releasing Peptide-2-Stimulated GH Secretion in Men
J. Clin. Endocrinol. Metab., September 1, 2004; 89(9): 4581 - 4587.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
A. J. van der Lely, M. Tschop, M. L. Heiman, and E. Ghigo
Biological, Physiological, Pathophysiological, and Pharmacological Aspects of Ghrelin
Endocr. Rev., June 1, 2004; 25(3): 426 - 457.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
C. Y. Bowers, R. Granda, S. Mohan, J. Kuipers, D. Baylink, and J. D. Veldhuis
Sustained Elevation of Pulsatile Growth Hormone (GH) Secretion and Insulin-Like Growth Factor I (IGF-I), IGF-Binding Protein-3 (IGFBP-3), and IGFBP-5 Concentrations during 30-Day Continuous Subcutaneous Infusion of GH-Releasing Peptide-2 in Older Men and Women
J. Clin. Endocrinol. Metab., May 1, 2004; 89(5): 2290 - 2300.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
F. Obal Jr., J. Alt, P. Taishi, J. Gardi, and J. M. Krueger
Sleep in mice with nonfunctional growth hormone-releasing hormone receptors
Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2003; 284(1): R131 - R139.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Interv.Home page
H. Hosoda, M. Kojima, and K. Kangawa
Ghrelin and the Regulation of Food Intake and Energy Balance
Mol. Interv., December 1, 2002; 2(8): 494 - 503.
[Abstract] [Full Text]

Home page
 J. Clin. Endocrinol. Metab.Home page
S. M. Anderson, L. Wideman, J. T. Patrie, A. Weltman, C. Y. Bowers, and J. D. Veldhuis
E2 Supplementation Selectively Relieves GH's Autonegative Feedback on GH-Releasing Peptide-2-Stimulated GH Secretion
J. Clin. Endocrinol. Metab., December 1, 2001; 86(12): 5904 - 5911.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
R. G. Gondo, M. H. Aguiar-Oliveira, C. Y. Hayashida, S. P. A. Toledo, N. Abelin, M. A. Levine, C. Y. Bowers, A. H. O. Souza, R. M. C. Pereira, N. L. Santos, et al.
Growth Hormone-Releasing Peptide-2 Stimulates GH Secretion in GH-Deficient Patients with Mutated GH-Releasing Hormone Receptor
J. Clin. Endocrinol. Metab., July 1, 2001; 86(7): 3279 - 3283.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
M. Maghnie, B. Salati, S. Bianchi, M. Rallo, C. Tinelli, M. Autelli, G. Aimaretti, and E. Ghigo
Relationship between the Morphological Evaluation of the Pituitary and the Growth Hormone (GH) Response to GH-Releasing Hormone Plus Arginine in Children and Adults with Congenital Hypopituitarism
J. Clin. Endocrinol. Metab., April 1, 2001; 86(4): 1574 - 1579.
[Abstract] [Full Text]

Home page
 J. Clin. Endocrinol. Metab.Home page
S. M. Anderson, N. Shah, W. S. Evans, J. T. Patrie, C. Y. Bowers, and J. D. Veldhuis
Short-Term Estradiol Supplementation Augments Growth Hormone (GH) Secretory Responsiveness to Dose-Varying GH-Releasing Peptide Infusions in Healthy Postmenopausal Women
J. Clin. Endocrinol. Metab., February 1, 2001; 86(2): 551 - 560.
[Abstract] [Full Text]

Home page
 DiabetesHome page
M. Shintani, Y. Ogawa, K. Ebihara, M. Aizawa-Abe, F. Miyanaga, K. Takaya, T. Hayashi, G. Inoue, K. Hosoda, M. Kojima, et al.
Ghrelin, an Endogenous Growth Hormone Secretagogue, Is a Novel Orexigenic Peptide That Antagonizes Leptin Action Through the Activation of Hypothalamic Neuropeptide Y/Y1 Receptor Pathway
Diabetes, February 1, 2001; 50(2): 227 - 232.
[Abstract] [Full Text]

Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
L. Wideman, J. Y. Weltman, J. T. Patrie, C. Y. Bowers, N. Shah, S. Story, A. Weltman, and J. D. Veldhuis
Synergy of L-arginine and growth hormone (GH)-releasing peptide-2 on GH release: influence of gender
Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2000; 279(4): R1455 - R1466.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
L. Wideman, J. Y. Weltman, J. T. Patrie, C. Y. Bowers, N. Shah, S. Story, J. D. Veldhuis, and A. Weltman
Synergy of L-arginine and GHRP-2 stimulation of growth hormone in men and women: modulation by exercise
Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2000; 279(4): R1467 - R1477.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
A.-C. A. R. Pinto, M. R. D. Silva, M. R. Martins, E. Brunner, and A.-M. J. Lengyel
Effects of Short-Term Glucocorticoid Deprivation on Growth Hormone (GH) Response to GH-Releasing Peptide-6: Studies in Normal Men and in Patients with Adrenal Insufficiency
J. Clin. Endocrinol. Metab., April 1, 2000; 85(4): 1540 - 1544.
[Abstract] [Full Text]

Home page
 EndocrinologyHome page
A. Tivesten, E. Bollano, K. Caidahl, V. Kujacic, X. Y. Sun, T. Hedner, A. Hjalmarson, B.-A. Bengtsson, and J. Isgaard
The Growth Hormone Secretagogue Hexarelin Improves Cardiac Function in Rats after Experimental Myocardial Infarction
Endocrinology, January 1, 2000; 141(1): 60 - 66.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
M. Gasperi, G. Aimaretti, G. Scarcello, G. Corneli, C. Cosci, E. Arvat, E. Martino, and E. Ghigo
Low Dose Hexarelin and Growth Hormone (GH)-Releasing Hormone as a Diagnostic Tool for the Diagnosis of GH Deficiency in Adults: Comparison with Insulin-Induced Hypoglycemia Test
J. Clin. Endocrinol. Metab., August 1, 1999; 84(8): 2633 - 2637.
[Abstract] [Full Text]

Home page
 EndocrinologyHome page
R. D. Kineman, J. Kamegai, and L. A. Frohman
Growth Hormone (GH)-Releasing Hormone (GHRH) and the GH Secretagogue (GHS), L692,585, Differentially Modulate Rat Pituitary GHS Receptor and GHRH Receptor Messenger Ribonucleic Acid Levels
Endocrinology, August 1, 1999; 140(8): 3581 - 3586.
[Abstract] [Full Text]

Home page
 J. Clin. Endocrinol. Metab.Home page
M. Korbonits, G. Kaltsas, L. A. Perry, P. Putignano, A. B. Grossman, G. M. Besser, and P. J. Trainer
The Growth Hormone Secretagogue Hexarelin Stimulates the Hypothalamo-Pituitary-Adrenal Axis via Arginine Vasopressin
J. Clin. Endocrinol. Metab., July 1, 1999; 84(7): 2489 - 2495.
[Abstract] [Full Text]

Home page
 Physiol. Rev.Home page
E. E. Muller, V. Locatelli, and D. Cocchi
Neuroendocrine Control of Growth Hormone Secretion
Physiol Rev, April 1, 1999; 79(2): 511 - 607.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
H. G. Maheshwari, A. Rahim, S. M. Shalet, and G. Baumann
Selective Lack of Growth Hormone (GH) Response to the GH-Releasing Peptide Hexarelin in Patients with GH-Releasing Hormone Receptor Deficiency
J. Clin. Endocrinol. Metab., March 1, 1999; 84(3): 956 - 959.
[Abstract] [Full Text]

Home page
 J. Clin. Endocrinol. Metab.Home page
E. Ghigo, L. Gianotti, E. Arvat, J. Ramunni, M. R. Valetto, F. Broglio, M. Rolla, F. Cavagnini, and E. E. Müller
Effects of Recombinant Human Insulin-Like Growth Factor I Administration on Growth Hormone (GH) Secretion, Both Spontaneous and Stimulated by GH-Releasing Hormone or Hexarelin, a Peptidyl GH Secretagogue, in Humans
J. Clin. Endocrinol. Metab., January 1, 1999; 84(1): 285 - 290.
[Abstract] [Full Text]

Home page
 Endocr. Rev.Home page
A. Giustina and J. D. Veldhuis
Pathophysiology of the Neuroregulation of Growth Hormone Secretion in Experimental Animals and the Human
Endocr. Rev., December 1, 1998; 19(6): 717 - 797.
[Abstract] [Full Text]

Home page
 J. Clin. Endocrinol. Metab.Home page
E. Arvat, R. Giordano, J. Ramunni, G. Arnaldi, A. Colao, R. Deghenghi, G. Lombardi, F. Mantero, F. Camanni, and E. Ghigo
Adrenocorticotropin and Cortisol Hyperresponsiveness to Hexarelin in Patients with Cushing's Disease Bearing a Pituitary Microadenoma, But Not in Those with Macroadenoma
J. Clin. Endocrinol. Metab., December 1, 1998; 83(12): 4207 - 4211.
[Abstract] [Full Text]

Home page
 J. Clin. Endocrinol. Metab.Home page
M. Maghnie, V. Spica-Russotto, M. Cappa, M. Autelli, C. Tinelli, P. Civolani, R. Deghenghi, F. Severi, and S. Loche
The Growth Hormone Response to Hexarelin in Patients with Different Hypothalamic-Pituitary Abnormalities
J. Clin. Endocrinol. Metab., November 1, 1998; 83(11): 3886 - 3889.
[Abstract] [Full Text]

Home page
 J. Clin. Endocrinol. Metab.Home page
P. F. Catalina, F. Mallo, M. A. Andrade, R. V. García-Mayor, and C. Diéguez
Growth Hormone (GH) Response to GH-Releasing Peptide-6 in Type 1 Diabetic Patients with Exaggerated GH-Releasing Hormone-Stimulated GH Secretion
J. Clin. Endocrinol. Metab., October 1, 1998; 83(10): 3663 - 3667.
[Abstract] [Full Text]

Home page
 EndocrinologyHome page
D. F. Carmignac, P. A. Bennett, and I. C. A. F. Robinson
Effects of Growth Hormone Secretagogues on Prolactin Release in Anesthetized Dwarf (dw/dw) Rats
Endocrinology, August 1, 1998; 139(8): 3590 - 3596.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
V. Mericq, F. Cassorla, T. Salazar, A. Avila, G. Iñiguez, C. Y. Bowers, and G. R. Merriam
Effects of Eight Months Treatment with Graded Doses of a Growth Hormone (GH)-Releasing Peptide in GH-Deficient Children
J. Clin. Endocrinol. Metab., July 1, 1998; 83(7): 2355 - 2360.
[Abstract] [Full Text]

Home page
 J. Clin. Endocrinol. Metab.Home page
D. Micic, V. Popovic, M. Doknic, D. Macut, C. Dieguez, and F. F. Casanueva
Preserved Growth Hormone (GH) Secretion in Aged and Very Old Subjects after Testing with the Combined Stimulus GH-Releasing Hormone plus GH-Releasing Hexapeptide-6
J. Clin. Endocrinol. Metab., July 1, 1998; 83(7): 2569 - 2572.
[Abstract] [Full Text]

Home page
 J. Clin. Endocrinol. Metab.Home page
I. Shimon and S. Melmed
Human Fetal Pituitary Expresses Functional GHRP Receptors--Authors' Responsee
J. Clin. Endocrinol. Metab., June 1, 1998; 83(6): 2216a - 2217.
[Full Text]

Home page
 J. Clin. Endocrinol. Metab.Home page
I. Shimon, X. Yan, and S. Melmed
Human Fetal Pituitary Expresses Functional Growth Hormone-Releasing Peptide Receptors
J. Clin. Endocrinol. Metab., January 1, 1998; 83(1): 174 - 178.
[Abstract] [Full Text]

Home page
 EndocrinologyHome page
P. A. Bennett, G. B. Thomas, A. D. Howard, S. D. Feighner, L. H. T. Van der Ploeg, R. G. Smith, and I. C. A. F. Robinson
Hypothalamic Growth Hormone Secretagogue-Receptor (GHS-R) Expression Is Regulated by Growth Hormone in the Rat
Endocrinology, November 1, 1997; 138(11): 4552 - 4557.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
R. G. Smith, L. H. T. Van der Ploeg, A. D. Howard, S. D. Feighner, K. Cheng, G. J. Hickey, M. J. Wyvratt Jr., M. H. Fisher, R. P. Nargund, and A. A. Patchett
Peptidomimetic Regulation of Growth Hormone Secretion
Endocr. Rev., October 1, 1997; 18(5): 621 - 645.
[Abstract] [Full Text]

Home page
 J. Clin. Endocrinol. Metab.Home page
I. M. Chapman, O. H. Pescovitz, G. Murphy, T. Treep, K. A. Cerchio, D. Krupa, B. Gertz, W. J. Polvino, E. H. Skiles, S. S. Pezzoli, et al.
Oral Administration of Growth Hormone (GH) Releasing Peptide-Mimetic MK-677 Stimulates the GH/Insulin-Like Growth Factor-I Axis in Selected GH-Deficient Adults
J. Clin. Endocrinol. Metab., October 1, 1997; 82(10): 3455 - 3463.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
S. Loche, A. Colao, M. Cappa, J. Bellone, G. Aimaretti, G. Farello, A. Faedda, G. Lombardi, R. Deghenghi, and E. Ghigo
The Growth Hormone Response to Hexarelin in Children: Reproducibility and Effect of Sex Steroids
J. Clin. Endocrinol. Metab., March 1, 1997; 82(3): 861 - 864.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 1995 by The Endocrine Society