GHRP-6
Growth Hormone Releasing Peptide-6, Growth hormone-releasing hexapeptide, His-D-Trp-Ala-Trp-D-Phe-Lys-NH2
Ghrelin and its unacylated isoform stimulate the growth of adrenocortical tumor cells via an anti-apoptotic pathway.
Delhanty. P J D PJ; van Koetsveld. P M PM; Gauna. C C; van de Zande. B B; Vitale. G G; Hofland. L J LJ; van der Lely. A J AJ
Key Findings
- Acylated and unacylated ghrelin at nanomolar levels double the proliferation of adrenal carcinoma cells.
- [D‑Lys(3)]GHRP‑6 (a GHRP‑6 analog) blocks the ghrelin‑induced growth of these tumor cells.
- Ghrelin suppresses apoptosis in the cancer cells, indicating an anti‑apoptotic signaling pathway.
Practical Outcomes
- For most biohackers, the data do not change everyday GHRP‑6 dosing for growth hormone boost, but they highlight a potential anti‑tumor benefit of GHRP‑6 in adrenal tissue. If you have a history of adrenal tumors or hyperplasia, you might want to discuss GHRP‑6 use with a medical professional. Overall, the findings are preliminary and limited to cell‑culture models, so they should be taken as a safety cue rather than a protocol change.
Summary
The study found that the hormone ghrelin (both its normal and a common inactive form) can make adrenal gland cancer cells grow faster by stopping them from dying, and that a synthetic peptide called GHRP‑6 can block this growth‑boosting effect. This suggests ghrelin may act like a self‑fuel for adrenal tumors, while GHRP‑6 can act as an antagonist in this specific context.
Abstract
Ghrelin is expressed in normal human adrenocortical cells and induces their proliferation through growth hormone secretagogue receptor 1a (GHS-R1a). Consequently, it was of interest to us to determine whether acylated ghrelin and its predominant serum isoform, unacylated ghrelin, also act as factors for adrenocortical carcinoma cell growth. To examine a potential ghrelin-regulated system in adrenocortical tumors, we measured proliferative effects of acylated and unacylated ghrelin in the adrenocortical carcinoma cell lines SW-13 and NCI-H295R. We also examined the expression of ghrelin, GHS-R1a, and corticotrophin-releasing factor receptor 2 (CRF-R2). Acylated and unacylated ghrelin in the nanomolar range dose-dependently induced adrenocortical cell growth up to 200% of untreated controls, as measured by thymidine uptake and WST1 assay. The proliferative effects of acylated and unacylated ghrelin in SW-13 cells was blocked by [D-Lys(3)]growth hormone-releasing peptide 6 (GHRP6), but a CRF-R2 antagonist had no effect on unacylated ghrelin growth stimulation. Cell cycle analysis suggests that acylated and unacylated ghrelin suppress the sub-G(0)/apoptotic fraction by up to 50%. Measurement of DNA fragmentation and caspase-3 and -7 activity in SW-13 cells confirmed that acylated and unacylated ghrelin suppress apoptotic rate. SW-13 cells express preproghrelin mRNA and secrete ghrelin, and [D-Lys(3)]GHRP6 suppresses their basal proliferation rate, strongly suggesting that ghrelin could act as an auto/paracrine growth factor. Acylated and unacylated ghrelin are potential auto/paracrine factors acting through an antiapoptotic pathway to stimulate adrenocortical tumor cell growth. Unacylated ghrelin-stimulated growth is suppressed by an antagonist of GHS-R1a, suggesting either that unacylated ghrelin is acylated before its action or that ghrelin, unacylated ghrelin, and [D-Lys(3)]GHRP-6 bind to a novel receptor in these cells.
Study Information
pubmed
2007
2007-04-03T00:00:00.000Z
10.1152/ajpendo.00377.2006