Abstract
For some time now, the authors have been investigating the neuroendocrine events leading to increased growth hormone (GH) secretion following administration of GH secretagogues, including GH-releasing peptide (GHRP-6). It is now well established that these compounds act both at the pituitary (1–5) and within the central nervous system (CNS) (6,7). The recent cloning of the GHRP-6 receptor has paved the way for the localization of the receptors at both pituitary and hypothalamic sites (8).
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References
Bowers CY, Momany FA, Reynolds GA, Hong A. On the in vitro and in vivo activity of a new synthetic hexapeptide that acts on the pituitary to specifically release growth hormone. Endocrinology 1984; 114: 1537 - 1545.
Bowers CY, Sartor AO, Reynolds GA, Badger TM. On the actions of the growth hormone-releasing hexapeptide, GHRP. Endocrinology 1991; 128, 2027 - 2035.
Smith RG, Cheng K, Schoen W, Pong S-S, Hickey G, Jacks T, Butler B, Chan WW-S, Chaung L-YP, Judith F, Taylor J, Wyvratt MJ, Fisher MH. A non-peptide growth hormone secretagogue. Science 1993; 260: 1640 - 1643.
Deghenghi R, Cananzi MM, Torsello A, Battisti C, Muller EE, Locatelli V. GH-releasing activity of hexarelin, a new growth-hormone releasing peptide, in infant and adult rats. Life Sci 1994; 54: 1321 - 1328.
McDowell RS, Elias KA, Stanley MS, Burdick DJ, Burnier IP, Chan KS, Fairbrother WJ, Hammonds RG, Ingle GS, Jacobsen NE, Mortensen DL, Rawson TE, Won WB, Clark RG, Somers TC. Growth-hormone secretagogues: characterization, efficacy, and minimal bioactive conformation. Proc Natl Acad Sci USA 1995;92:11, 165-11, 169.
Dickson SL, Leng G, Robinson ICAF. Systemic administration of growth hormone-releasing peptide (GHRP-6) activates hypothalamic arcuate neurones. Neuroscience 1993; 53: 303 - 306.
Dickson SL, Leng G, Dyball REJ, Smith RG. Central actions of peptide and non-peptide growth hormone secretagogues in the rat. Neuroendocrinology 1995; 61: 36 13.
Howard AD, Feighner SD, Cully DF, Arena JP, Liberator PA, Rosenblum CI, Hamelin M, Hrenluk DL, Palyha OC, Anderson J, Paress PS, Diaz C, Chou M, Liu KK, McKee KK, Pong S-S, Chaung L-Y, Elbrecht A, Dashkevicz M, Heavens R, Rigby M, Sirinathsinghji DJS, Dean DC, Melillo DG, Patchett AA, Nargund R, Griffin PR, DeMartino JA, Gupta SK, Schaeffer JM, Smith RG, Van der Ploeg LHT. A pituitary gland and hypothalamic receptor that functions in growth hormone release. Science 1996; 273: 974 - 977.
Clark RG, Carlsson LMS, Trojnar J, Robinson ICAF. The effects of a growth hormone-releasing peptide and growth hormone-releasing factor in conscious and anaesthetized rats. J Neuroendocrinol 1989; 1: 249 - 255.
Cheng K, Chan WWS, Barreto A, Convey EM, Smith RG. The synergistic effects of His-D- Trp-AlaTrp-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. Endocrinology 1989; 124: 2791 - 2798.
Fairhall KM, Mynett A, Smith RG, Robinson ICAF. Consistent GH responses to respeated injections of GH-releasing hexapeptide (GHRP-6) and the non-peptide GH secretagogue, L-692,585. J Endocrinol 1995; 145: 417 - 426.
Bailey ART, Leng G, Smith RG, Dickson SL. Growth hormone secretagogue activation of the arcuate nucleus and brainstem occurs via a non-noradrenergic pathway. J Neuroendocrinol (in press).
Hoffman GE, Lee WS, Attardi B, Yann V, Fitzsimmons MD. Luteinizing hormone-releasing hormone neurones express c-fos antigen after steroid activation. Endocrinology 1990; 126: 1736 - 1741.
Luckman SM, Dyball REJ, Leng G. Induction of c-fos expression in hypothalamic neurones requires synaptic activation and not simply increased spike activity. J Neurosci 1994; 14: 4825 - 4830.
Hamamura M, Leng G, Emson PC, Kiyama H. Electrical activation and c-fos mRNA expression in rat neurosecretory neurones after systemic administration of cholecystokinin. J Physiol 1991; 444: 51 - 63.
Guillaume V, Magnan E, Cataldi M, Dutour A, Sauze N, Renard M, Razafindraibe H, Conte-Devolx B, Deghenghi R, Lenaerts V, Oliver C. Growth hormone (GH)-releasing hormone secretion is stimulated by a new GH-releasing hexapeptide in sheep. Endocrinology 1994; 135: 1073 - 1076.
Dickson SL, Leng G, Robinson ICAF. Electrical stimulation of the rat periventricular nucleus influences the activity of hypothalamic neurones. J Neuroendocrinol 1994; 6: 359 - 367.
Hewson AK, Viltart O, McKenzie DN, Dyball REJ, Dickson SL. GHRP-6-induced changes in electrical activity of single cells in the arcuate, ventromedial and periventricular nuclei of a hypothalamic slice preparation in vitro. J Neuroendocrinol (in press).
Dickson SL, Doutrelant-Viltart O, McKenzie DN, Dyball REJ. Somatostatin inhibits arcuate neurones excited by GH-releasing peptide (GHRP-6) in rat hypothalamic slices. J Physiol 1996; 495P: 109 P.
Dickson SL, Luckman SM. Induction of c-fos messenger ribonucleic acid in neuropeptide Y and growth hormone (GH)-releasing factor neurones in the rat arcuate nucleus following systemic injection of the GH secretagogue, GH-releasing peptide-6. Endocrinology 1997; 138: 771 - 777.
Kamegai J, Hasegawa O, Minami S, Sugihara H Wakabayashi I. The growth hormone-releasing peptide KP-102 induces c-fos expression in the arcuate nucleus. Mol Brain Res 1996; 39: 153 - 159.
Clark JT, Kalra PS, Crowley WR, Kalra SP. Neuropeptide Y and human pancreatic polypeptide stimulate feeding in rats. Endocrinology 1984; 115: 427 - 429.
Locke W, Kirgis HD, Bowers CY, Abdoh AA. Intracerebroventricular growth hormone-releasing peptide-6 stimulates eating without affecting plasma growth hormone responses in rats. Life Sci 1995; 56: 1347 - 1352.
Dickson SL, Doutrelant-Viltart O, Dyball REJ, Leng G. Retrogradely labelled neurosecretory neurones of the rat hypothalamic arcuate nucleus express Fos protein following systemic injection of GH-releasing peptide-6. J Endocrinol 1996; 151: 323 - 331.
Huhn WC, Hartman ML, Pezzoli SS, Thorner MO. Twenty-four-hour growth hormone (GH)-releasing peptide (GHRP) infusion enhances pulsatile GH secretion and specifically attenuates the response to a subsequent GHRP bolus. J Clin Endo Metab 1993; 76: 1202 - 1208.
Gertz BJ, Barrett JS, Eisenhandler R, Krupa DA, Wittreich JM, Seibold JR, Schneider SH. Growth hormone response in man to L-692,429, a novel nonpeptide mimic of growth hormone-releasing peptide. J Clin Endo Metab 1993; 77: 1393 - 1397.
Weltman A, Weltman JY, Schurrer R, Evans WS, Veldhuis JD, Rogol AD. Endurance training amplifies the pulsatile release of growth hormone: effects of training intensity. J Appl Physiol 1992; 72: 2188 - 2196.
Luger A, Watschinger B, Deuster P, Svoboda T, Clodi M, Chrousos GP. Plasma growth hormone and prolactin responses to acute exercise and to a lactate infusion. Neuroendocrinology 1992; 56: 112 - 117.
Moretti C, Fabria GL, Cappa A, Calzolari A, Frailoi F, Grossman A, Besser G. Naloxone inhibits exercise-induced release of prolactin and growth hormone in athletes. Clin Endocrinol 1983; 18: 135 - 141.
Casanueva FF, Villanueva L, Dieguez C, Diaz Y, Cabranes JA, Szoke B, Scanlon MF, Schally AV, Fernandez-Cruz A. Free fatty acids block growth hormone (GH) releasing hormone-stimulated GH secretion in man directly at the pituitary. J Clin Endo Metab 1987; 65: 634 - 642.
Okada K, Sugihara H, Minami S, Wakabayashi I. Effect of parenteral administration of selected nutrients and central injection of y-globulin from antiserum to Neuropeptide Y on growth hormone secretory pattern in food-deprived rats. Neuroendocrinology 1993; 57: 678 - 686.
Tannenbaum GS, Martin JB. Evidence for an endogenous ultradian rhythm governing growth hormone secretion in the rat. Endocrinology 1976; 98: 562 - 570.
Bruno JF, Song J, Berelowitz M. Regulation of rat hypothalamic preprogrowth hormone-releasing factor messenger ribonucleic acid by dietary protein. Endocrinology 1991; 129: 1226 - 1232.
Patchett AA, Nargund RP, Tata JR, Chen MH, Barakat KJ, Johnston DBR, Cheng K, Chan WWS, Butler B, Hickey G, Jacks T, Schleim K, Pong S-S, Chaung L-YP, Chen H-Y, Frazier E, Leung KH, Chiu SHL, Smith RG. Design and biological-activities ofl-163,191 (MK-0677)-a potent, orally-active growth-hormone secretagogue. PNAS 1995; 92: 7001 - 7005.
Lin S-C, Lin CR, Gukovsky I, Lusis AJ, Sawchenko PE, Rosenfeld MG. Molecular basis of the little mouse phenotype and implications for cell type-specific growth. Nature 1993; 364: 208 - 213.
Jansson J-O, Downs TR, Beamer WG, Frohman LA. Receptor associated resistance to growth hormone-releasing hormone in dwarf “little” mice. Science 1986; 232: 511 - 512.
Jansson J-O, Downs TR, Beamer WG, Frohman LA. The dwarf “little” (lit/lit) mouse is resistant to growth hormone (GH)-releasing peptide (GH-RP-6) as well as to GH-releasing hormone (GRH). Proc 68th Ann Meet Endo Soc, Anaheim, 1986; P397.
Dickson SL, Doutrelant-Viltart O, Leng G. Growth hormone (GH)-deficient dw/dw rats and lit/lit mice show increased Fos expression in the hypothalamic arcuate nucleus following systemic injection of GH-releasing peptide (GHRP-6). J Endocrinol 1995; 146: 519 - 526.
Torsello A, Luoni M, Grilli R, Guidi M, Wehrenberg WB, Deghenghi R, Muller EE, Locatelli V. Hexarelin stimulation of growth hormone release and mRNA levels in an infant and adult rat model of impaired GHRH function. Neuroendocrinol 1997; 65: 91 - 97.
Wehrenberg WB, Ling N, Bölem P, Esch F, Brazeau P, Guillemin R. Physiological roles of somatocrinin and somatostatin in the regulation of growth hormone secretion. Biochem Biophys Res Commun 1982; 109: 562 - 567.
Clark RG, Robinson ICAF. Growth hormone responses to multiple injections of a human growth hormone-releasing factor in conscious male and female rats. J Endocrinol 1985; 106: 281 - 289.
Eden S. Age-and sex-related differences in episodic growth hormone secretion in the rat. Endocrinology 1979; 105: 555 - 560.
Saunders A, Terry LC, Audet J, Brazeau P, Martin JB. Dynamic studies of growth hormone and prolactin secretion in the female rat. Neuroendocrinology 1976; 21: 193 - 203.
Jansson J-O, Ekberg S, Isaksson OGP, Edén S. Influence of gonadal steroids on age-and sex-related secretory patterns of growth hormone in the rat. Endocrinology 1984; 114: 1287 - 1294.
Herbison AE. Sexually dimorphic expression of androgen receptor immunoreactivity by somatostatin neurons in rat hypothalamic periventricular nucleus and bed nucleus of the stria terminalis. J Neuroendocrinol 1995; 7: 543 - 553.
Clark RG, Carlsson LMS, Rafferty B, Robinson ICAF. The rebound release of growth hormone (GH) following somatostatin infusion in rats involves hypothalamic growth hormone-releasing factor release. J Endocrinol 1988; 119: 397 - 404.
Okada K, Wakabayashi I, Sugihara H, Minami S, Kitamura T, Yamada J. Electrical stimulation of hypothalamic periventricular nucleus is followed by a large rebound secretion of growth hormone in unanesthetized rats. Neuroendocrinology 1991; 53: 306 - 312.
Epelbaum J, Moyse E, Tannenbaum GS, Kordon C, Beaudet A. Combined autoradiographic and immunohistochemical evidence for an association of somatostatin binding sites with growth hormone-releasing factor-containing nerve cell bodies in the rat arcuate nucleus. J Neuroendocrinol 1989; 1: 109 - 115.
Bertherat J, Dournaud P, Bérod A, Normand E, Bloch B, Rostène W, Kordon C, Epelbaum J. Growth hormone-releasing hormone-synthesising neurones are a subpopulation of somatostatin receptor-labelled cells in the rat arcuate nucleus—a combined in situ hybridisation and receptor light-microscopic autoradiographic study. Neuroendocrinology 1992; 56: 25 - 31.
Fairhall KM, Mynett A, Robinson ICAF. Central effects of growth hormone-releasing hexapeptide (GHRP-6) on growth hormone release are inhibited by central somatostatin action. J Endocrinol 1995; 144: 555 - 560.
Dickson SL, Bailey ART, Doutrelant-Viltart O, Dyball REJ, Leng G. The induction of Fos protein in cells of the rat hypothalamic arcuate nucleus in response to GHRP-6 administration is attenuated by sandostin. Neuroendocrinology 1997; 66: 188 - 194.
Brazeau P, Vale WW, Burgus R, Ling N, Butcher M, Rivier J, Guillemin R. Hypothalamic polypeptide that inhibits the secretion of immunoreactive pituitary growth hormone. Science 1973; 179: 77 - 79.
Fukata J, Diamond DJ, Martin JB. Effects of rat growth hormone (rGH)-releasing factor and somatostatin on the release and synthesis of rGH in dispersed pituitary cells. Endocrinology 1985; 117: 457 - 467.
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Dickson, S.L., Leng, G. (2000). Central Actions of Peptide and Nonpeptide Growth Hormone Secretagogues. 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_5
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DOI: https://doi.org/10.1007/978-1-59259-015-5_5
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