GHRP-6 as a potent GH and appetite stimulant
- 05-20-2006, 03:19 AM
GHRP-6 as a potent GH and appetite stimulant
Influence of sex, age and adrenergic pathways on the growth hormone response to GHRP-6.
Penalva A, Pombo M, Carballo A, Barreiro J, Casanueva FF, Dieguez C.
Department of Medicine, Faculty of Medicine, University of Santiago de Compostela, Spain.
------->His-dTrp-Ala-Trp-dPhe-Lys-NH2 (GHRP-6) is a synthetic compound that releases GH in a dose-related and specific manner in several species including man. To further characterize the effects of GHRP-6 on GH secretion in normal human subjects, we assessed plasma GH levels following GHRP-6 administration in normal male adult subjects, normal female adult subjects at different stages of their menstrual cycle and in normal prepubertal male and female children. We also studied the influence of adrenergic pathways on GHRP-6 induced GH secretion in normal adult male subjects. DESIGN: In a group of eight volunteers the following tests were carried out: GHRP-6 alone (1 microgram/kg i.v. at 0 minutes); propranolol (40 mg p.o. at -30 minutes) plus GHRP-6; and prazosin (3 mg p.o. at -120 minutes) plus GHRP-6. Another group of eight volunteers were studied with GHRP-6 as above; clonidine alone (300 mg p.o. at -60 minutes); and clonidine plus GHRP-6. A group of nine women were studied with 1 microgram/kg i.v. of GHRP-6 at 0 minutes, at different stages of their menstrual cycle. Finally, 12 children were studied with GHRP-6 using the same dose and methods as above. PATIENTS: Twenty-five normal adult subjects (16 male and nine female) and 12 normal prepubertal children (six male and six female) wer studied after giving informed consent. MEASUREMENTS: Plasma GH levels were measured by radioimmunoassay. RESULTS: No differences in GH responses to GHRP-6 were found between children and normal adult male or female subjects at different stages of their menstrual cycle. Administration of propranolol and clonidine did not modify the GH responses to GHRP-6 in male adults. In contrast, prazosin administration induced an increase in plasma GH levels that was statistically different from that of GHRP-6 alone (. < 0.05 between area under curve). CONCLUSIONS: GHRP-6 exerts a potent stimulatory effect on GH secretion in adults and children. Its effects, at least at the dose studied, are independent of sex and age. Noradrenergic pathways through alpha 2 adrenergic receptors are unlikely to influence this response.
Massive growth hormone (GH) discharge in obese subjects after the combined administration of GH-releasing hormone and GHRP-6: evidence for a marked somatotroph secretory capability in obesity
F Cordido, A Penalva, C Dieguez and FF Casanueva
Endocrine Section Hospital General de Galicia, Santiago de Compostela, Spain.
------->GH secretion in response to all provocative stimuli is decreased in patients with obesity. However, the precise mechanism causing this impairment in GH release is unknown. His-DTrp-Ala-Trp-DPhe-Lys-NH2 (GHRP-6) is a synthetic compound that releases GH in a dose-related and specific manner in several species, including man. To gain further insight into disrupted GH secretion in obesity, GHRP-6 and GH-releasing hormone (GHRH) at a dose of 100 micrograms, i.v., were administered either alone or in combination in a group of 19 obese subjects. In a group of obese patients, GHRP-6 induced GH secretion, with a GH peak (mean +/- SEM) of 15.7 +/- 4.4 micrograms/L and an area under the curve (AUC) of 674 +/- 187, which were larger than those after GHRH stimulation (6.8 +/- 1.1 and 412 +/- 71, respectively). Enhancement of the endogenous cholinergic tone was obtained in another group of obese subjects by means of pyridostigmine (120 mg, orally). Pyridostigmine administered 60 min before GHRP-6, increased both the mean GH peak (32.2 +/- 6.9) and the AUC (1413 +/- 537) after GHRP-6 administration. In a separate group of subjects, the combined administration of GHRP-6 and GHRH induced a massive discharge of GH, with individual responses ranging from 14-86 micrograms/L. GHRP-6 plus GHRH induced a mean GH peak of 42.2 +/- 10.9 and an AUC of 1894 +/- 784 (P < 0.05), clearly indicating a potentiating (synergic) action when the two compounds were administered together. These data show that GH responses to GHRP-6 were almost twice those to GHRH in obese patients. The stimulatory effect exerted by pyridostigmine on GHRP-6-induced GH secretion supported the view of increased somatostatinergic tone in obesity. Finally, the massive GH discharge that followed the administration of GHRH plus GHRP- 6 was not observed after any stimulus in obesity, clearly indicating that the impaired GH secretion is a functional and potentially reversible state.
Intracerebroventricular growth-hormone-releasing peptide-6 stimulates eating without affecting plasma growth hormone responses in rats.
Locke W, Kirgis HD, Bowers CY, Abdoh AA.
Department of Internal Medicine, Ochsner Clinic, New Orleans, Louisiana 70121, USA.
------->The purpose of this study was to determine the effect of intracerebroventricular (i.c.v.) injections of a synthetic, opioid-related hexapeptide, growth-hormone-releasing peptide-6 (GHRP-6), on stimulation of eating by rats and to correlate this aspect of feeding behavior with the peripheral plasma growth hormone (GH) response to the administered peptide. GHRP-6 dissolved in 5 microL of saline was injected into the lateral ventricles of sated, adult, male, Sprague-Dawley rats in doses from 0 pmol (saline only) to 1000 pmol. For 1 hour after injection, the occurrence of eating was noted, and specimens of arterial blood were collected at 0, 15, 30, and 60 minutes. The plasma was assayed for GH. A nearly linear, statistically significant (p < 0.01) dose-response relationship between the dose of GHRP-6 and the incidence of eating was noted. The mean change from baseline of plasma GH during the 60 minutes after injection was not dose-related (p > 0.2, p > 0.1, and p > 0.1 at 15, 30, and 60 minutes, respectively). We conclude that GHRP-6 given intracerebroventricularly to sated, adult, male, Sprague-Dawley rats stimulates eating and suggest that it does so by some mechanism that is independent of its GH-releasing property.
Central effects of growth hormone-releasing hexapeptide (GHRP-6) on growth hormone release are inhibited by central somatostatin action
KM Fairhall, A Mynett, and IC Robinson
------->Growth hormone (GH) release is stimulated by a variety of synthetic secretagogues, of which growth hormone-releasing hexapeptide (GHRP-6) has been most thoroughly studied; it is thought to have actions at both pituitary and hypothalamic sites. To evaluate the central actions of this peptide, we have studied GH release in response to direct i.c.v. injections in anaesthetized guinea pigs. GHRP-6 (0.04-1 microgram) stimulated GH release > 10-fold 30-40 min after i.c.v. injection. The same GH response required > 20-fold more GHRP-6 when given by i.v. injection. GH release could also be elicited by a non-peptide GHRP analogue (L-692,585, 1 microgram i.c.v.), whereas a growth hormone-releasing factor (GRF) analogue (human GRF27Nle(1-29)NH2, 2 micrograms, i.c.v.) was ineffective. A long acting somatostatin analogue (Sandostatin, SMS 201-995, 10 micrograms i.c.v.) (SMS) given 20 min before 200 ng GHRP-6 blocked GH release. This was unlikely to be due to a direct effect of SMS leaking out to the pituitary, since central SMS injections did not affect basal GH release, nor did they block GH release in response to i.v. GRF injections. We conclude that the hypothalamus is a major target for GHRP-6 in vivo. Since the GH release induced by central GHRP-6 injections can be inhibited by a central action of somatostatin, and other data indicate that GHRP-6 activates GRF neurones, we suggest that somatostatin may block this activation via receptors known to be located on or near the GRF cells themselves. Somatostatin may therefore be a functional antagonist of GHRP-6 acting centrally, as well as at the pituitary gland.
Oral activity of the growth hormone releasing peptide His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 in rats, dogs and monkeys.
Walker RF, Codd EE, Barone FC, Nelson AH, Goodwin T, Campbell SA.
Department of Toxicology, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406-0939.
------->The purpose of this study was to evaluate the growth hormone (GH) releasing activity of orally administered His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 (GHRP-6, SK&F 110679) in rats, dogs and monkeys. Rats were administered GHRP-6 orally by gavage or parenterally through femoral artery catheters. Blood was collected before and after GHRP-6 administration for estimation of plasma GH and comparison of GH changes resulting from enteral and parenteral administration of the peptide. GHRP-6 was administered to dogs intravenously (i.v.) through cephalic vein catheters, intragastrically (i.g.) through esophagostomy tubes or intraduodenally (i.d.) through vascular access ports, and blood was collected before and after peptide administration for estimation of plasma GH. Cynomolgus monkeys were administered GHRP-6 i.g., and blood was collected from abdominal aorta for estimation of changes in plasma GH. Enteral activity of GHRP-6 was observed in all 3 species tested. In rats, ED50's for enteral and parenteral administration of GHRP-6 were 4 mg/kg and 28 micrograms/kg, respectively. Thus in rats, enterally administered GHRP-6 was 0.7% as bioactive as the parenterally administered peptide. In dogs GHRP-6 was slightly less potent than in rats, with ED50's for i.g. and i.v. administration approximately 15 mg/kg and 125 micrograms/kg, respectively. However, enteral potency of GHRP-6 in dogs was 0.8% of parenteral potency, and thus, comparable to that in rats. Additionally, comparison of plasma GH levels following i.g. vs i.d. administration in dogs suggested greater activity by the i.d. route. Monkeys were the species most sensitive to enterally administered GHRP-6, with plasma GH increased in those receiving i.g. doses as low as 0.3 mg/kg and an ED50 of 0.75 mg/kg compared to 4 and 15 mg/kg in rats and dogs, respectively. The results of this study demonstrate that GHRP-6 releases GH when administered directly into the gastrointestinal tract. Although enteral activity is approximately 1% of parenteral activity, GHRP-6 is potent, especially in primates which require relatively low doses to provoke GH release. These data suggest that orally active GHRP-6 may provide a practical therapeutic alternative to parenterally administered peptides such as GHRH, especially if enteral activity is enhanced with appropriate formulation.PharmD
- 05-20-2006, 12:30 PM
So what I got from this is that the doses of this should be quite low, correct? The one study it was like only 1mcg and the other the max dose was something like 80mcg. This could be very good as a 1mg vial could last quite long. I think....
- 05-20-2006, 12:48 PM
Originally Posted by idunk42
The study that interested me the most, however, was the study that showed GHRP-6 + GHRH raised levels as high as 86 ug/L as opposed to ~16 ug/L for the GHRP-6 only group and ~7 for the GHRH only group. They seem to work very synergistically. I sent a message to IBE about GHRH. Who knows, maybe it will be available one day. Either way, though, GHRP-6 looks promising and that study conducted to check oral bioavailability seemed that it works in that manner, which is also nice.PharmD
05-20-2006, 05:38 PM
Originally Posted by LakeMountD
The only study that I have come across that addressed dosing in human subjects used 2mcg/kg of lean body weight...if that's the case it could get pretty pricey...I am planning on trying 100mcg/ed, maybe split in 2 doses 5on/2off...I've been trying to find something that states the half life though....
Yeah, I also read that oral availability is good.....I wonder if IBE can get GHRP-2 (not that we don't appreciate the -6)...evidently, GHRP-2 is much more potent and is actually EQUALLY as potent as GHRH....And there is probably a better possibility of getting the -2 than the GHRH....which would lead me to believe that using the -2 and the -6 together would yield comparable results....
Hang on, let me see if I can find some of the info to post (It was about a month ago that I found a lot of this stuff, and like a dumbazz I didn't save or bookmark any of it)....
05-24-2006, 11:25 AM
The $1,000,000 question is: which would be superior for us older members looking for longetivey/body recomposition issues that attract us to GH in the first place--Pgh or Ghrp-6?
From this read it would seem like the Ghrp is the better choice--or am I comparing apples and oranges?
05-24-2006, 12:32 PM
I have read studies where the GHRH alone, failed to provide continous results past something like 12 weeks.
HOwever, GHRH is available if you look for it. (I realize it's not GHRP-6, but you had mentioned GHRH.).
For interesting GHRH administration technique (plasma based) see here : http://www.advisys.net/html/ghrh_applications.html
Another quick glance at dosing and results found here: http://www.bioresearchonline.com/con...&VNETCOOKIE=NO
Another somthin somthin..
Orexins are recently discovered neuropeptides that play an important role in the regulation of hormone secretion, and their receptors have been recently demonstrated in the pituitary..... http://endo.endojournals.org/cgi/con...ll/143/12/4609
Looks like 1000ug runs maybe $130.00 (synthetiic).
Certificate of Analysis and Data Sheet
Human Growth Hormone Releasing Hormone (rHuGHRH)
E.Coli Catalog No.
Synthetic Human GHRH is a single, non-glycosylated, polypeptide chain containing 29 amino acids and having a molecular mass of 3358 Dalton. Corresponds to the amino-terminal segment of the naturally occurring human growth hormone-releasing hormone consisting of 44 amino acid residues.
rHuGHRH is purified by proprietary chromatographic techniques.
Sterile Filtered White lyophilized (freeze-dried) powder.
The protein (1mg/ml) was lyophilized after extensive dialyses against 1.7mg sodium phosphate buffer (0.1 mg sodium phosphate monobasic & 1.6mg sodium phosphate dibasic).
It is recommended to reconstitute the lyophilized GHRH in sterile 18MΩ-cm H2O not less than 100µg/ml, which can then be further diluted to other aqueous solutions.
Lyophilized GHRH although stable at room temperature for 3 weeks, should be stored desiccated below -18 C. Upon reconstitution GHRH should be stored at 4 C between 2-7 days and for future use below -18 C. For long term storage it is recommended to add a carrier protein (0.1% HSA or BSA).
Please avoid freeze-thaw cycles.
Greater than 98.0% as determined by:
(a) Analysis by RP-HPLC.
(b) Anion-exchange FPLC.
(c) Analysis by reducing and non-reducing SDS-PAGE Silver Stained.
Amino-Acid Sequence :
The sequence of the first five N-terminal amino acids was determined and was found to be Tyr-Ala-Asp-Ala-Ile.
Dimers and aggregates:
Less than 1% as determined by silver-stained SDS-PAGE gel analysis.
ProSpec's HuGHRH is fully biologically active, increases plasma growth hormone concentrations by directly stimulating the anterior pituitary gland to release natural human growth hormone.
Less than 0.1 ng/µg (IEU/µg) of GHRH.
Protein quantitation was carried out by two independent methods:
1. UV spectroscopy at 280 nm.
2. Analysis by RP-HPLC, using a calibrated solution of GHRH as a Reference Standard.
Prospec's products are furnished for LABORATORY RESEARCH USE ONLY. The product may not be used as drugs, agricultural or pesticidal products, food additives or household chemicals.
Somatoliberin precursor (Growth hormone-releasing factor)
(Growth hormone-releasing hormone)
Belongs to the glucagon family.
I had this information left over from a related search I was doing a little while ago. Unfortunitaly, most of my studies (along with the one showing the deminished results from GHRH after something like 8-12 weeks I deleated)
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