Explore studies of ghrp.
L-692,429 (0.001-1.0 mg/kg IV) produced dose-dependent GH release in healthy young men. At 1 mg/kg, response was comparable to GHRH-(1-29). Safe and well tolerated.
Gertz, B J; Barrett, J S; Eisenhandler, R; Krupa, D A; Wittreich, J M; Seibold, J R; Schneider, S H · RCT
Hexarelin effectively stimulated growth hormone secretion in both infant and adult rats through a non-GHRH pathway.
Deghenghi, R; Cananzi, M M; Torsello, A; Battisti, C; Muller, E E; Locatelli, V · Animal Study
L-692,585 produced 4.3 to 7-fold increases in peak GH with maintained efficacy over 15 days of daily dosing and elevated IGF-1 by day 15.
Jacks, T; Hickey, G; Judith, F; Taylor, J; Chen, H; Krupa, D; Feeney, W; Schoen, W; Ok, D; Fisher, M · Animal Study
Both GHRP-6 and non-peptide GH secretagogues activated Fos expression in the arcuate nucleus and excited arcuate neuroendocrine neurons, confirming central brain actions.
Dickson, S L; Leng, G; Dyball, R E; Smith, R G · Animal Study
Novel backbone-modified GH secretagogues with molecular weight under 500 were the most potent reported, with confirmed anabolic efficacy and a defined bioactive conformation.
McDowell, R S; Elias, K A; Stanley, M S; Burdick, D J; Burnier, J P; Chan, K S; Fairbrother, W J; Hammonds, R G; Ingle, G S; Jacobsen, N E; Mortensen, D L; Rawson, T E; Won, W B; Clark, R G; Somers, T C · Animal Study
MK-0677 was characterized as the most potent orally active GH secretagogue, with EC50 of 1.3 nM in vitro, oral efficacy in dogs at 0.125 mg/kg, and confirmed anabolic effects in rodents.
Patchett, A A; Nargund, R P; Tata, J R; Chen, M H; Barakat, K J; Johnston, D B; Cheng, K; Chan, W W; Butler, B; Hickey, G · Animal Study
GHRP-2 was considerably more potent than GHRP-6 at stimulating GH release through PKC-dependent pathways, and both caused crosstalk with the cAMP pathway in gsp oncogene-expressing tumors.
Adams, E F; Lei, T; Buchfelder, M; Bowers, C Y; Fahlbusch, R · In Vitro
GHRPs stimulate growth hormone release through a receptor distinct from GHRH, acting at both the pituitary and hypothalamic level, with consistent effects demonstrated across species and administration routes.
Argente, J; García-Segura, L M; Pozo, J; Chowen, J A · Review
KP-102 induces c-fos expression specifically in the arcuate nucleus, and this occurs even in hypophysectomized rats, confirming a direct hypothalamic site of action.
Kamegai, J; Hasegawa, O; Minami, S; Sugihara, H; Wakabayashi, I · Animal Study
Hexarelin maintained GH-releasing efficacy with repeated administration, and hexarelin plus GHRH produced a synergistic GH response exceeding individual effects.
Massoud, A F; Hindmarsh, P C; Matthews, D R; Brook, C G · RCT
The GH secretagogue receptor was solubilized as a ~255 kDa receptor-ligand-G-protein complex from porcine pituitary, confirming it is distinct from the GHRH receptor.
Pomés, A; Pong, S S; Schaeffer, J M · In Vitro
A specific high-affinity G-protein-linked receptor for GH secretagogues was identified, operating through a distinct signaling pathway from GHRH.
Pong, S S; Chaung, L Y; Dean, D C; Nargund, R P; Patchett, A A; Smith, R G · In Vitro
GH secretagogues act through a novel receptor at dual sites (hypothalamus and pituitary) to amplify natural pulsatile GH release rather than creating continuous artificial elevation.
Smith, R G; Pong, S S; Hickey, G; Jacks, T; Cheng, K; Leonard, R; Cohen, C J; Arena, J P; Chang, C H; Drisko, J; Wyvratt, M; Fisher, M; Nargund, R; Patchett, A · Review
GHRP-2 maintained GH-releasing efficacy in critically ill patients despite blunted responses to GHRH, suggesting a preserved alternative pathway for GH stimulation.
Van den Berghe, G; de Zegher, F; Bowers, C Y; Wouters, P; Muller, P; Soetens, F; Vlasselaers, D; Schetz, M; Verwaest, C; Lauwers, P; Bouillon, R · RCT
GHRP-2 increased intracellular cAMP (like GHRH) while GHRP-6 released GH without raising cAMP, revealing partially different mechanisms despite similar GH-releasing outcomes.
Wu, D; Chen, C; Zhang, J; Bowers, C Y; Clarke, I J · In Vitro
GHRP-2 and hexarelin both showed potent GH-releasing activity with slight stimulatory effects on prolactin, ACTH, and cortisol; their GH-releasing activities were directly compared for the first time.
Arvat, E; di Vito, L; Maccagno, B; Broglio, F; Boghen, M F; Deghenghi, R; Camanni, F; Ghigo, E · RCT
GHRP-2 stimulation revealed significant residual GH secretory potential in children classified as GH-deficient, with peak responses varying by growth disorder type.
Bercu, B B; Walker, R F · Clinical Trial
GHRP-2 and GHRP-6 each synergize with GRF/GHRH but combining both GHRPs at maximal doses adds no further GH release, confirming shared receptor competition.
Cheng, J; Wu, T J; Butler, B; Cheng, K · In Vitro
Octreotide (somatostatin analog) attenuated GH secretagogue-induced Fos expression in the arcuate nucleus, showing somatostatin opposes GHRP action centrally.
Dickson, S L; Viltart, O; Bailey, A R; Leng, G · Animal Study
Hexarelin's GH-releasing effect is significantly modulated by somatostatin tone, with somatostatin withdrawal amplifying the GH response to hexarelin.
Massoud, A F; Hindmarsh, P C; Brook, C G · Clinical Trial
GH secretagogue receptors are molecularly confirmed in both pituitary and hypothalamus, using a distinct signal transduction pathway from GHRH.
McKee, K K; Palyha, O C; Feighner, S D; Hreniuk, D L; Tan, C P; Phillips, M S; Smith, R G; Van der Ploeg, L H; Howard, A D · In Vitro
Intranasal GHRP-2 effectively stimulated GH release in children with short stature, demonstrating viability of a needle-free delivery route.
Pihoker, C; Badger, T M; Reynolds, G A; Bowers, C Y · Clinical Trial
GH secretagogues activate hypothalamic neurons and require an intact GHRH system for full in vivo potency, despite being able to release GH directly from the pituitary.
Robinson, I C · Review
GHRH and GHRPs can restore GH secretion in aging and disease, addressing the visceral fat accumulation and metabolic changes associated with GH decline.
Thorner, M O; Chapman, I M; Gaylinn, B D; Pezzoli, S S; Hartman, M L · Review
Continuous GHRH plus GHRP-2 infusion partially restored GH pulsatility and substantially raised IGF-1 levels in critically ill patients with suppressed somatotropic axes.
Van den Berghe, G; de Zegher, F; Veldhuis, J D; Wouters, P; Awouters, M; Verbruggen, W; Schetz, M; Verwaest, C; Lauwers, P; Bouillon, R; Bowers, C Y · Clinical Trial
Prolonged critical illness disrupts spontaneous TSH and prolactin secretion, and GH secretagogue infusion affects these hormones alongside GH stimulation.
Van den Berghe, G; de Zegher, F; Veldhuis, J D; Wouters, P; Gouwy, S; Stockman, W; Weekers, F; Schetz, M; Lauwers, P; Bouillon, R; Bowers, C Y · Clinical Trial
GRF and GHRP-2 both require PKC translocation for GH release, while GHRP-6 releases GH through a PKC-independent mechanism in ovine somatotrophs.
Wu, D; Clarke, I J; Chen, C · In Vitro
SSTR2 knockout mice showed no growth hormone negative feedback on arcuate nucleus neurons, demonstrating that this receptor subtype is essential for GH autoregulation.
Zheng, H; Bailey, A; Jiang, M H; Honda, K; Chen, H Y; Trumbauer, M E; Van der Ploeg, L H; Schaeffer, J M; Leng, G; Smith, R G · Animal Study
GHS-R type 1a (active) and type 1b (inactive) mRNA was detected in human pituitary tumor tissue and rat GH3 cells via RT-PCR, confirming these tumors express the GHRP receptor.
Adams, E F; Huang, B; Buchfelder, M; Howard, A; Smith, R G; Feighner, S D; van der Ploeg, L H; Bowers, C Y; Fahlbusch, R · In Vitro
MK-0677 induced c-Fos expression in arcuate nucleus neurons in vivo, confirming direct hypothalamic activation as a mechanism for its GH-releasing effect.
Bailey, A R; Smith, R G; Leng, G · Animal Study
Phenyl piperazine-based peptidomimetics were identified as potent, orally active GH secretagogues by mimicking privileged structural motifs from known GH-releasing compounds.
Barakat, K J; Cheng, K; Chan, W W; Butler, B S; Jacks, T M; Schleim, K D; Hora, D F; Hickey, G J; Smith, R G; Patchett, A A; Nargund, R P · In Vitro
GHRPs release GH through a unique dual and complementary mechanism acting on both the hypothalamus and pituitary, via a specific receptor distinct from the GHRH receptor.
Bowers, C Y · Review
Pulsatile hexarelin dosing maintained GH-releasing efficacy with modest desensitization, while continuous infusion caused marked attenuation of GH response, supporting intermittent dosing strategies.
Conley, L K; Gaillard, R C; Giustina, A; Brogan, R S; Wehrenberg, W B · Animal Study
GH secretagogues function as somatostatin antagonists at the hypothalamic-pituitary level and can restore youthful GH secretion patterns in elderly subjects.
Fuh, V L; Bach, M A · Review
Oral GH secretagogues effectively increase GH and IGF-1 through a specific receptor, with clinical potential spanning GH deficiency, aging, and catabolic states, though their optimal therapeutic role remained to be defined.
Ghigo, E; Arvat, E; Camanni, F · Review
Ipamorelin demonstrated approximately 20% nasal bioavailability in rats, superior to GHRP-2, GHRP-6, and two other peptides, supporting its potential for non-invasive nasal delivery.
Johansen, P B; Hansen, K T; Andersen, J V; Johansen, N L · Animal Study
GH secretagogues like GHRP-6 and hexarelin can stimulate growth hormone release through mechanisms distinct from GHRH, making them potentially useful for thalassemia patients with iron-damaged pituitary glands.
Karydis, I; Tolis, A; Tolis, G · Review
Specific, high-affinity binding sites for GH secretagogues were identified in the human pituitary and multiple brain regions including hypothalamus and hippocampus, indicating CNS effects beyond GH release.
Muccioli, G; Ghè, C; Ghigo, M C; Papotti, M; Arvat, E; Boghen, M F; Nilsson, M H; Deghenghi, R; Ong, H; Ghigo, E · In Vitro
Multiple GHRP receptor subtypes exist in the pituitary, brain, and heart, with hexarelin binding cardiac tissue — explaining the cardiovascular effects of GH secretagogues beyond their GH-releasing activity.
Ong, H; Bodart, V; McNicoll, N; Lamontagne, D; Bouchard, J F · Review
Photoaffinity labeling with modified hexarelin identified a specific GHRP receptor protein in pituitary membranes, confirming the existence of a distinct GH secretagogue receptor subtype.
Ong, H; McNicoll, N; Escher, E; Collu, R; Deghenghi, R; Locatelli, V; Ghigo, E; Muccioli, G; Boghen, M; Nilsson, M · In Vitro
KP-102 stimulated food intake in freely-fed but not fasted or stressed rats, and central somatostatin administration blocked this effect, demonstrating state-dependent appetite modulation by GH secretagogues.
Shibasaki, T; Yamauchi, N; Takeuchi, K; Ishii, S; Sugihara, H; Wakabayashi, I · Animal Study
GHRP receptor mRNA was detected in human fetal pituitary by RT-PCR, and GHRP-2 stimulated dose-dependent GH release from cultured fetal pituitary cells, demonstrating functional GH secretagogue receptors are present before birth.
Shimon, I; Yan, X; Melmed, S · In Vitro
GHRP-2 combined with TRH infusion reduced elevated leptin levels and reactivated suppressed GH and thyroid axes in prolonged critically ill patients, addressing the paradoxical fat-gain/muscle-wasting metabolic state.
Van den Berghe, G; Wouters, P; Carlsson, L; Baxter, R C; Bouillon, R; Bowers, C Y · RCT
Combined GHRP-2 and TRH infusion most effectively reactivated both pulsatile GH secretion and the thyrotropic axis in 20 prolonged critically ill patients, with effects exceeding either agent alone.
Van den Berghe, G; de Zegher, F; Baxter, R C; Veldhuis, J D; Wouters, P; Schetz, M; Verwaest, C; Van der Vorst, E; Lauwers, P; Bouillon, R; Bowers, C Y · RCT
Chronic central GH secretagogue infusion upregulated NPY and GHRH gene expression in the arcuate nucleus while altering Fos expression patterns, demonstrating neuroplastic adaptations to sustained receptor stimulation.
Bailey, A R; Giles, M; Brown, C H; Bull, P M; Macdonald, L P; Smith, L C; Smith, R G; Leng, G; Dickson, S L · Animal Study
GHRH pretreatment and morphine both attenuated GH secretagogue-induced Fos expression in the arcuate nucleus, demonstrating negative feedback and opioid-GH system crosstalk in GH secretagogue signaling.
Bailey, A R; Honda, K; Smith, R G; Leng, G · Animal Study
GHS-R was expressed in 28 of 30 pituitary adenomas across all subtypes, not just GH-secreting tumors. Functional studies showed GH secretagogues stimulated hormone release from multiple tumor types in culture.
Barlier, A; Zamora, A J; Grino, M; Gunz, G; Pellegrini-Bouiller, I; Morange-Ramos, I; Figarella-Branger, D; Dufour, H; Jaquet, P; Enjalbert, A · In Vitro
A novel cardiac-specific GHRP receptor distinct from the pituitary GHS-R was identified in rat heart tissue, binding hexarelin with high affinity and mediating cardioprotective effects independently of GH release.
Bodart, V; Bouchard, J F; McNicoll, N; Escher, E; Carrière, P; Ghigo, E; Sejlitz, T; Sirois, M G; Lamontagne, D; Ong, H · Animal Study
GH secretagogues have clinically significant non-endocrine effects including cardiovascular protection, orexigenic (appetite-stimulating) activity, sleep architecture improvement, and potential anti-aging properties mediated by widespread GHS receptor distribution.
Ghigo, E; Arvat, E; Broglio, F; Giordano, R; Gianotti, L; Muccioli, G; Papotti, M; Graziani, A; Bisi, G; Deghenghi, R; Camanni, F · Review
Oral GHRP-2 (5-10 mg/kg) stimulated significant GH release in 1-month-old goats (peak at 15 min) but not in 3-month-old goats, demonstrating age-dependent oral peptide bioavailability in ruminants.
Hashizume, T; Kawai, M; Ohtsuki, K; Ishii, A; Numata, M · Animal Study