Characterization of Growth Hormone Secretion to Growth Hormone-releasing Peptide-2 in Domestic Animals - A Review

Growth hormone-releasing peptide-2 (GHRP-2, also named KP102) is a new hexapeptide of a series of synthetic growth hormone-releasing peptides (GHRPs) which stimulates the secretion of growth hormone (GH) in vitro and in vivo in several species including calf, sheep and pig. The GH-releasing activity of GHRP-2 is two to three times more effective than that of the original GHRP-6, and GHRP-1 in the rats and humans. To date, GHRP-2 seems to be the most potent member of the family of GHRPs. Since the GHRPs are short peptides (5-7 amino acid residues), they are synthesized easily and are not as readily degraded in plasma as GH- releasing hormone (GHRH). These features ameliorate their potential on domestic animals because of their chemical nature the GHRPs are efficacious when administered i.v. orally or orally. However, studies in cow, pig and sheep do not indicate such a close relationship between GHRH, somatostatin (SS) and GH, calling into question the general applicability of the human and rat models. Perhaps there is an important role for an endogenous GHRP in the regulation of GH secretion in domestic animals. This review provides an overview on the current knowledge of physiological role of GHRP-2 in domestic animals. (Asian-Aust. J. Anim. Sci. 2002. Vol 15, No. 5 : 757 -766)

[1]  S. Hidaka,et al.  Effects of the administration of growth hormone-releasing peptide-2 (GHRP-2) orally by gavage and in feed on growth hormone release in swine. , 2001, Domestic animal endocrinology.

[2]  K. Kangawa,et al.  Ghrelin stimulates gastric acid secretion and motility in rats. , 2000, Biochemical and biophysical research communications.

[3]  H. G. Lee,et al.  The effect of growth hormone-releasing peptide-2 (KP102) administration on plasma insulin-like growth factor (IGF)-1 and IGF-binding proteins in Holstein steers on different planes of nutrition. , 2000, Domestic animal endocrinology.

[4]  H. Inoue,et al.  The effects of growth hormone-releasing peptide-2 (GHRP-2) on the release of growth hormone and growth performance in swine. , 2000, Domestic animal endocrinology.

[5]  M. Nakazato,et al.  Ghrelin is a growth-hormone-releasing acylated peptide from stomach , 1999, Nature.

[6]  C. Mcmahon,et al.  Feeding-induced increases in insulin do not suppress secretion of growth hormone. , 1999, Domestic animal endocrinology.

[7]  E. Müller,et al.  Six-week treatment with hexarelin in young dogs: evaluation of the GH responsiveness to acute hexarelin or GHRH administration, and of the orexigenic effect of hexarelin. , 1999, European journal of endocrinology.

[8]  T. Hashizume,et al.  Oral administration of peptidergic growth hormone (GH) secretagogue KP102 stimulates GH release in goats. , 1999, Domestic animal endocrinology.

[9]  G. Van den Berghe,et al.  Growth hormone-releasing peptide-2 infusion synchronizes growth hormone, thyrotrophin and prolactin release in prolonged critical illness. , 1999, European journal of endocrinology.

[10]  V. Locatelli,et al.  Novel hexarelin analogs stimulate feeding in the rat through a mechanism not involving growth hormone release. , 1998, European journal of pharmacology.

[11]  C. Strasburger,et al.  A five day treatment with daily subcutaneous injections of growth hormone-releasing peptide-2 causes response attenuation and does not stimulate insulin-like growth factor-I secretion in healthy young men. , 1998, European journal of endocrinology.

[12]  S. Roh,et al.  Effects of muscarinic and adrenergic blockade on growth hormone secretion induced by growth hormone-releasing peptide-2 (GHRP-2) in ovariectomized ewes. , 1997, Endocrine journal.

[13]  S. Mohan,et al.  Insulin-like growth factor-binding proteins in serum and other biological fluids: regulation and functions. , 1997, Endocrine reviews.

[14]  S. Roh,et al.  No desensitization of the growth hormone (GH) response between GH-releasing peptide-2 and GH-releasing factor in calves. , 1997, Journal of animal science.

[15]  S. Roh,et al.  Mechanisms of action of growth hormone-releasing peptide-2 in bovine pituitary cells. , 1997, Journal of animal science.

[16]  R. Nugent,et al.  Circulating insulin-like growth factor I, insulin-like growth factor binding proteins, growth hormone, and resumption of estrus in postpartum cows subjected to dietary energy restriction. , 1997, Journal of animal science.

[17]  R. Heap,et al.  The effect of bovine somatotropin and diet on somatotropin binding sites in hepatic tissue of lactating dairy cows. , 1997, Journal of dairy science.

[18]  浩一 佐々木,et al.  新しい成長ホルモン放出ペプチド(KP102)のヤギ成長ホルモン放出効果 , 1997 .

[19]  S. Ishii,et al.  Intracerebroventricular administration of the growth hormone-releasing peptide KP-102 increases food intake in free-feeding rats. , 1996, Endocrinology.

[20]  S. Grottoli,et al.  Short-term administration of intranasal or oral Hexarelin, a synthetic hexapeptide, does not desensitize the growth hormone responsiveness in human aging. , 1996, European journal of endocrinology.

[21]  H. Tucker,et al.  5-Hydroxytryptaminergic Receptor-Mediated Regulation of Growth Hormone Secretion in Holstein Steers Occurs via α2-Adrenergic-Dependent and -Independent Mechanisms , 1996, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[22]  Patrick R. Griffin,et al.  A Receptor in Pituitary and Hypothalamus That Functions in Growth Hormone Release , 1996, Science.

[23]  S. Roh,et al.  Characteristics of growth hormone secretion responsiveness to growth hormone-releasing peptide-2 (GHRP-2 or KP102) in calves. , 1996, Endocrine journal.

[24]  I. Clarke,et al.  Growth hormone-releasing hormone and somatostatin concentrations in the hypophysial portal blood of conscious sheep during the infusion of growth hormone-releasing peptide-6. , 1996, Domestic animal endocrinology.

[25]  R. Campbell,et al.  Ovarian expression of insulin-like growth factor-I (IGF-I), IGF binding proteins, and growth hormone (GH) receptor in heifers actively immunized against GH-releasing factors. , 1996, Endocrinology.

[26]  I. Clarke,et al.  Signal transduction systems employed by synthetic GH-releasing peptides in somatotrophs. , 1996, The Journal of endocrinology.

[27]  C. Bowers,et al.  The effects of GH-releasing peptide-6 (GHRP-6) and GHRP-2 on intracellular adenosine 3',5'-monophosphate (cAMP) levels and GH secretion in ovine and rat somatotrophs. , 1996, The Journal of endocrinology.

[28]  S. Pong,et al.  Identification of a new G-protein-linked receptor for growth hormone secretagogues. , 1996, Molecular endocrinology.

[29]  D. Johnston,et al.  Design and biological activities of L-163,191 (MK-0677): a potent, orally active growth hormone secretagogue. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[30]  C. Bowers,et al.  Intracerebroventricular growth-hormone-releasing peptide-6 stimulates eating without affecting plasma growth hormone responses in rats. , 1995, Life sciences.

[31]  V. Locatelli,et al.  Mechanism of action of hexarelin and GHRP-6: analysis of the involvement of GHRH and somatostatin in the rat. , 1995, Neuroendocrinology.

[32]  R. Dyball,et al.  Central actions of peptide and non-peptide growth hormone secretagogues in the rat. , 1995, Neuroendocrinology.

[33]  P. Gluckman,et al.  A homologous radioimmunoassay for ovine insulin-like growth factor-binding protein-2: ontogenesis and the response to growth hormone, placental lactogen and insulin-like growth factor-I treatment in sheep. , 1995, The Journal of endocrinology.

[34]  S. Grottoli,et al.  Growth hormone-releasing activity of growth hormone-releasing peptide-6 is maintained after short-term oral pretreatment with the hexapeptide in normal aging. , 1994, European journal of endocrinology.

[35]  J. Taylor,et al.  Effects of acute and repeated intravenous administration of L-692,585, a novel non-peptidyl growth hormone secretagogue, on plasma growth hormone, IGF-1, ACTH, cortisol, prolactin, insulin, and thyroxine levels in beagles. , 1994, The Journal of endocrinology.

[36]  H. Sugihara,et al.  Effect of d-Ala-d-βNal-Ala-Trp-d-Phe-Lys-NH2 (KP-102) on GH secretion in urethan-anesthetized rats , 1994, Regulatory Peptides.

[37]  J. Willoughby,et al.  Constitutive growth hormone secretion in sheep after hypothalamopituitary disconnection and the direct in vivo pituitary effect of growth hormone releasing peptide 6. , 1994, Neuroendocrinology.

[38]  V. Lenaerts,et al.  Growth hormone-releasing activity of hexarelin, a new synthetic hexapeptide, after intravenous, subcutaneous, intranasal, and oral administration in man. , 1994, The Journal of clinical endocrinology and metabolism.

[39]  J. Taylor,et al.  Efficacy and specificity of L-692,429, a novel nonpeptidyl growth hormone secretagogue, in beagles. , 1994, Endocrinology.

[40]  I. Clarke,et al.  The effect of GH-releasing peptide-2 (GHRP-2 or KP 102) on GH secretion from primary cultured ovine pituitary cells can be abolished by a specific GH-releasing factor (GRF) receptor antagonist. , 1994, The Journal of endocrinology.

[41]  A. Barkan,et al.  Effects of a prolonged growth hormone (GH)-releasing peptide infusion on pulsatile GH secretion in normal men. , 1993, The Journal of clinical endocrinology and metabolism.

[42]  S. Schneider,et al.  Growth hormone response in man to L-692,429, a novel nonpeptide mimic of growth hormone-releasing peptide-6. , 1993, The Journal of clinical endocrinology and metabolism.

[43]  R. Campbell,et al.  Changes in serum somatotropin, somatotropin mRNA, and serum and follicular insulin-like growth factor-I in response to feed restriction in cows actively immunized against growth hormone-releasing factor. , 1993, Journal of animal science.

[44]  R. Campbell,et al.  Effect of feed restriction on serum somatotropin, insulin-like growth factor-I-(IGF-I) and IGF binding proteins in cyclic heifers actively immunized against growth hormone releasing factor. , 1993, Domestic animal endocrinology.

[45]  C. Diéguez,et al.  Influence of endogenous cholinergic tone and alpha-adrenergic pathways on growth hormone responses to His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 in the dog. , 1993, The Journal of endocrinology.

[46]  S. Pong,et al.  A nonpeptidyl growth hormone secretagogue. , 1993, Science.

[47]  M. Fisher,et al.  Stimulation of growth hormone release from rat primary pituitary cells by L-692,429, a novel non-peptidyl GH secretagogue. , 1993, Endocrinology.

[48]  M. Thorner,et al.  Twenty-four-hour growth hormone (GH)-releasing peptide (GHRP) infusion enhances pulsatile GH secretion and specifically attenuates the response to a subsequent GHRP bolus. , 1993, The Journal of clinical endocrinology and metabolism.

[49]  R. Pearson,et al.  A synthetic opioid peptide increases plasma growth hormone and prolactin in Holstein calves. , 1993, Journal of animal science.

[50]  C. Bowers.  GH Releasing Peptides - Structure and Kinetics , 1993, The Journal of pediatric endocrinology.

[51]  F. Casanueva,et al.  Effect of growth hormone (GH)-releasing hormone (GHRH), atropine, pyridostigmine, or hypoglycemia on GHRP-6-induced GH secretion in man. , 1993, The Journal of clinical endocrinology and metabolism.

[52]  M. Thorner,et al.  Oral administration of growth hormone (GH)-releasing peptide stimulates GH secretion in normal men. , 1992, The Journal of clinical endocrinology and metabolism.

[53]  R. Harvey,et al.  Effect of prepartum administration of growth hormone-releasing factor on somatotropin, insulin-like growth factor I, milk production, and postpartum return to ovarian activity in primiparous beef heifers. , 1992, Journal of animal science.

[54]  D. Bauman,et al.  Regulation of insulin-like growth factor-binding proteins in serum and lymph of lactating cows by somatotropin. , 1992, Endocrinology.

[55]  C. Bowers,et al.  The growth hormone-releasing activity of a synthetic hexapeptide in normal men and short statured children after oral administration. , 1992, The Journal of clinical endocrinology and metabolism.

[56]  C. E. Lyons,et al.  Pituitary adenylate cyclase activating polypeptide, growth hormone (GH)-releasing peptide and GH-releasing hormone stimulate GH release through distinct pituitary receptors. , 1992, Endocrinology.

[57]  P. Gluckman,et al.  Ontogenic differences in the nutritional regulation of circulating IGF binding proteins in sheep plasma. , 1992, Acta endocrinologica.

[58]  D. Clemmons,et al.  Nutrient balance and stage of lactation affect responses of insulin, insulin-like growth factors I and II, and insulin-like growth factor-binding protein 2 to somatotropin administration in dairy cows. , 1991, The Journal of nutrition.

[59]  D. Clemmons,et al.  Secretion and biological actions of insulin‐like growth factor binding proteins in two human tumor‐derived cell lines in vitro , 1991, Journal of cellular physiology.

[60]  P. Gluckman,et al.  Plasma IGF-I binding proteins in sheep: effect of recombinant growth hormone treatment and nutritional status. , 1991, Domestic animal endocrinology.

[61]  M. Thorner,et al.  Growth hormone (GH) secretion during continuous infusion of GH-releasing peptide: partial response attenuation. , 1991, The Journal of clinical endocrinology and metabolism.

[62]  T. Badger,et al.  On the actions of the growth hormone-releasing hexapeptide, GHRP. , 1991, Endocrinology.

[63]  A. M. Camoratto,et al.  Effect of lead on TRH and GRF binding in rat anterior pituitary membranes. , 1991, Toxicology.

[64]  T. Mcfadden,et al.  Effects of plane of nutrition, growth hormone and unsaturated fat on growth hormone, insulin and prolactin receptors in prepubertal lambs. , 1990, Journal of animal science.

[65]  F. Buonomo,et al.  The neurophysiological regulation of growth hormone secretion. , 1990, Domestic animal endocrinology.

[66]  L. Frohman,et al.  Measurement of growth hormone-releasing hormone and somatostatin in hypothalamic-portal plasma of unanesthetized sheep. Spontaneous secretion and response to insulin-induced hypoglycemia. , 1990, The Journal of clinical investigation.

[67]  C. Farmer,et al.  Effect of dose and frequency of administration of a potent analog of human growth hormone-releasing factor on hormone secretion and growth in pigs. , 1990, Journal of animal science.

[68]  M. Thorner,et al.  Growth hormone (GH)-releasing peptide stimulates GH release in normal men and acts synergistically with GH-releasing hormone. , 1990, The Journal of clinical endocrinology and metabolism.

[69]  S. Speciale,et al.  Interaction between norepinephrine and serotonin in the neuroendocrine control of growth hormone release in the rat. , 1990, Endocrinology.

[70]  F. Barone,et al.  Oral activity of the growth hormone releasing peptide His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 in rats, dogs and monkeys. , 1990, Life sciences.

[71]  E. Froesch,et al.  Insulin-like growth factors I and II in healthy man. Estimations of half-lives and production rates. , 1989, Acta endocrinologica.

[72]  A. Shu,et al.  Binding of a growth hormone releasing hexapeptide to specific hypothalamic and pituitary binding sites , 1989, Neuropharmacology.

[73]  S. Zinn,et al.  Effects of infusions of various doses of bovine growth hormone-releasing factor on blood hormones and metabolites in lactating Holstein cows. , 1989, The Journal of endocrinology.

[74]  I. Robinson,et al.  The Effects of a Growth Hormone‐Releasing Peptide and Growth Hormone‐Releasing Factor in Conscious and Anaesthetized Rats , 1989, Journal of neuroendocrinology.

[75]  D. Bauman,et al.  Temporal pattern of insulin-like growth factor-I response to exogenous bovine somatotropin in lactating cows. , 1989, Domestic animal endocrinology.

[76]  E. Convey,et al.  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. , 1989, Endocrinology.

[77]  A. Trenkle.  Influence of feeding on growth hormone secretion and response to growth hormone-releasing factor in sheep. , 1989, The Journal of nutrition.

[78]  L. F. Krabill,et al.  Food intake alters the serum growth hormone response to bovine growth hormone-releasing factor in meal-fed Holstein steers. , 1988, The Journal of endocrinology.

[79]  A. Grossman,et al.  GH FEEDBACK OCCURS THROUGH MODULATION OF HYPOTHALAMIC SOMATOSTATIN UNDER CHOLINERGIC CONTROL: STUDIES WITH PYRIDOSTIGMINE AND GHRH , 1987, Clinical endocrinology.

[80]  H. Lapierre,et al.  Dose response of two synthetic human growth hormone-releasing factors on growth hormone release in heifers and pigs. , 1987, Journal of animal science.

[81]  E. Müller.  Neural control of somatotropic function. , 1987, Physiological reviews.

[82]  J. Willoughby,et al.  Activation of serotonin receptors in the medial basal hypothalamus stimulates growth hormone secretion in the unanesthetized rat , 1987, Brain Research.

[83]  D. Marple,et al.  Effects of parachlorophenylalanine, quipazine and cyproheptadine on growth hormone and adrenocorticotropin secretion in steers. , 1987, Domestic animal endocrinology.

[84]  H. Imura,et al.  Involvement of growth hormone (GH)-releasing factor in GH secretion induced by serotoninergic mechanisms in conscious rats. , 1986, Endocrinology.

[85]  F. Buonomo,et al.  Growth hormone secretory responsiveness to multiple injections of growth hormone-releasing factor in sheep , 1986 .

[86]  F. Momany,et al.  Variables determining the growth hormone response of His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 in the rat. , 1985, Endocrinology.

[87]  A. Simmonds,et al.  Effect of different growth hormone-releasing factors on the concentrations of growth hormone, insulin and metabolites in the plasma of sheep maintained in positive and negative energy balance. , 1985, The Journal of endocrinology.

[88]  J. B. Martin,et al.  The effects of growth hormone (GH)-releasing peptides on GH secretion in perifused pituitary cells of adult male rats. , 1984, Endocrinology.

[89]  F. Momany,et al.  On the in vitro and in vivo activity of a new synthetic hexapeptide that acts on the pituitary to specifically release growth hormone. , 1984, Endocrinology.

[90]  F. Momany,et al.  Conformational energy studies and in vitro and in vivo activity data on growth hormone-releasing peptides. , 1984, Endocrinology.