Study summary · research use only
Natural (ghrelin) and synthetic (hexarelin) GH secretagogues stimulate H9c2 cardiomyocyte cell proliferation
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
This in vitro study used the H9c2 cardiomyocyte cell line (species not specified in the abstract) to test whether the GH secretagogues hexarelin and ghrelin affect cell proliferation. Hexarelin stimulated thymidine incorporation dose-dependently, with a significant response at 3 microM (147% of control) and a maximal response around 30 microM, appearing after 12 hours and peaking at 18 hours (176% of control). Ghrelin also increased thymidine incorporation (129% of control at 3 microM, 18 hours). The analogues Tyr-Ala-hexarelin and EP80317 showed comparable stimulation, while EP51389 and MK-0677 did not. Binding assays using labeled Tyr-Ala-hexarelin showed displacement by hexarelin, Tyr-Ala-hexarelin, EP80317, and ghrelin, while MK-0677 and EP51389 showed little displacement at 1 microM. The authors suggest a cardiac GHS binding site distinct from the pituitary.
Abstract
Recent experimental data demonstrate cardiovascular effects of the GH secretagogues (GHSs) hexarelin and ghrelin, the proposed natural ligand for the GHS receptor. Moreover, specific cardiac binding sites for GHSs have been suggested. The aim of the present study was to investigate if the natural ligand ghrelin and synthetic GHS peptide hexarelin and analogues have direct effects on the cardiomyocyte cell line, H9c2. Hexarelin stimulated thymidine incorporation in a dose-dependent manner with significant responses at 3 micro M (147+/-3% of control, P<0.01) and elicited maximal effects at concentrations around 30 micro M. This activity was seen already after 12 h of incubation with a maximal effect after 18 h (176+/-9% of control, P<0.01). Ghrelin also had a significant stimulatory effect on thymidine incorporation (129+/-2% of control at 3 micro M and 18 h, P<0.05). The stimulatory effect on thymidine incorporation of hexarelin, Tyr-Ala-hexarelin, EP80317 and ghrelin was specific and no stimulatory effect was observed with the truncated GH-releasing peptide EP51389 or the non-peptidyl GHS MK-0677. In competitive binding studies, (125)I-labeled Tyr-Ala-hexarelin was used as radioligand and competition curves showed displacement with hexarelin, Tyr-Ala-hexarelin, EP80317 and ghrelin, whereas MK-0677 and EP51389 produced very little displacement at 1 micro M concentration, adding further support for an alternative subtype binding site in the heart compared with the pituitary. In conclusion, we have demonstrated a dose-dependent and specific stimulation of cardiomyocyte thymidine incorporation by natural and synthetic GHS analogues, suggesting increased cell proliferation and binding of GHS to H9c2 cardiomyocyte cell membranes. These findings support potential peripheral effects of GHS on the cardiovascular system independent of an increased GH secretion.
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