GHRP-6
Growth Hormone Releasing Peptide-6, Growth hormone-releasing hexapeptide, His-D-Trp-Ala-Trp-D-Phe-Lys-NH2
Effects of coadministered growth hormone (GH)-releasing hormone and GH-releasing hexapeptide on maladaptive aspects of obesity in Zucker rats.
Bercu. B B BB; Yang. S W SW; Masuda. R R; Hu. C S CS; Walker. R F RF
Key Findings
- Co‑administering GHRH (3 µg/kg) and GHRP‑6 (300 µg/kg) for 60 days increased pituitary weight and basal GH concentrations in obese rats.
- Stimulated GH secretion remained lower in obese rats than in lean rats, indicating a resistance likely driven by high IGF‑1 levels.
- In adult obese rats, the peptide combo did not affect food intake or body‑weight gain, but it improved glucose tolerance.
- Plasma cholesterol rose in obese rats receiving the peptides, while IGF‑1 and insulin stayed high regardless of treatment.
Practical Outcomes
- For biohackers, using GHRP‑6 (especially with a GHRH analog) may help improve glucose handling but is unlikely to cause weight loss in already‑grown adults and could raise cholesterol. Obese individuals may be less responsive to GH secretagogues because of IGF‑1 feedback, so higher or longer dosing might be needed, but monitoring lipid profiles is advisable.
Summary
In obese Zucker rats, giving a daily combo of GHRH and GHRP‑6 boosted pituitary size and overall GH levels, but the rats still released less GH when stimulated compared to lean rats. The treatment didn’t change how much the adult rats ate or gained weight, but it did improve their ability to handle glucose, while also raising blood cholesterol. The findings suggest that obesity creates a resistance to these GH‑boosting peptides, likely because high IGF‑1 feeds back and blocks further GH release.
Abstract
The purpose of this study was to determine the effect of chronic pharmacological stimulation of the pituitary gland on GH hyposecretion and other maladaptive aspects of obesity. Obese Zucker rats were coadministered GH-releasing hormone (GHRH; 3 micrograms/kg) and GH-releasing hexapeptide (GHRP-6; 300 micrograms/kg), a potent combination of synergistic GH secretagogues, once daily for 60 consecutive days. Although pituitary weights and GH concentrations were higher in obese rats administered the peptides than in obese rats administered saline, stimulated GH secretion was lower in obese rats than in lean rats. However, compared to those in lean rats, plasma insulin-like growth factor-I and insulin concentrations were higher in the obese rats regardless of treatment. The GH secretagogues did not alter food intake or body weight gain in sexually mature obese rats, whereas body weight gain was significantly increased when they were administered to prepubertal obese rats. Although glucose tolerance was impaired in both groups of obese rats, it improved in obese rats administered GHRH and GHRP-6 compared to that in obese rats administered saline. On the other hand, plasma cholesterol concentrations were elevated in obese rats administered the GH secretagogues but not saline. In conclusion, the results of this study suggest that hyposensitivity to GHRH and GHRP-6 in obese Zucker rats results from high concentrations of plasma insulin-like growth factor-I that negatively feedback on stimulated GH secretion. Nonetheless, daily episodes of endogenous GH secretion resulting from chronic coadministration of GH secretagogues significantly influenced the pituitary gland as well as lipid and carbohydrate metabolism.
Study Information
pubmed
1992
10.1210/endo.131.6.1446617