GHRP-6
Growth Hormone Releasing Peptide-6, Growth hormone-releasing hexapeptide, His-D-Trp-Ala-Trp-D-Phe-Lys-NH2
Isolation and characterization of the 5'-flanking region of the growth hormone secretagogue receptor gene from black seabream Acanthopagrus schlegeli.
Yeung. Chung-Man CM; Chan. Chi-Bun CB; Cheng. Christopher H K CH
Key Findings
- A 2.1 kb promoter region of the seabream GHSR gene was isolated and characterized.
- Specific DNA segments (-514/+19 and -928/-515) act as key regulatory elements for gene expression.
- A GHSR agonist (similar to GHRP‑6) increases promoter activity in seabream cells, an effect blocked by a GHSR antagonist, indicating a positive feedback loop unlike the negative feedback seen in humans.
Practical Outcomes
- For biohackers, this study mainly highlights species differences in how GHSR agonists like GHRP‑6 may regulate their own receptor gene. It doesn’t provide direct guidance for human dosing or protocols, but suggests that the feedback mechanisms observed in fish may not translate to humans.
Summary
Researchers mapped the DNA region that controls the growth hormone secretagogue receptor (GHSR) gene in a fish called black seabream and found that activating the receptor with a GHSR agonist boosts its own gene activity, which is the opposite of what happens in humans.
Abstract
Ghrelin, the recently discovered endogenous ligand for growth hormone secretagogue receptor (GHSR), is widely expressed and involved in regulating diverse physiological functions in addition to stimulation of growth hormone (GH) secretion. Previous studies have demonstrated the functional significance of the ghrelin/GHSR system, yet the transcriptional regulation of the ghrelin and GHSR genes are poorly understood. We have recently cloned the GHSR cDNA from the pituitary of black seabream Acanthopagrus schlegeli. In the present study, we have isolated a 2.1 kb 5'-flanking region of the GHSR gene from the same species and have investigated, for the first time, the transcriptional regulation of GHSR from a non-human species. The 5'-flanking region of the seabream GHSR gene was found to contain a number of unique putative transcription factor-binding sites different from the human counterpart. Functional characterization of the 5'-flanking region in several cell lines indicates that the region between -1423 and +19 contains sufficient elements for promoter function. Moreover, progressive 3'-deletion analysis suggests the presence of negative regulatory element(s) and essential cis-acting element(s) at -514/+19 and -928/-515, respectively. Furthermore, we have shown that the promoter activity is significantly enhanced by a GHSR agonist in a cell line stably expressing the seabream GHSR, and this stimulatory effect could be completely blocked by a GHSR antagonist. These results suggest that homologous up-regulation plays an important role in the transcriptional control of the teleostean GHSR gene. This is in big contrast to the human situation in which a homologous down-regulation of the GHSR gene transcription by its own ligand has been previously demonstrated.
Study Information
pubmed
2004
2004-08-31T00:00:00.000Z
10.1016/j.mce.2004.06.005
13
39