Zinc ions increase GH signaling ability through regulation of available plasma membrane-localized GHR.

It is well known that zinc ion (Zn2+ ) can regulate the biological activity of growth hormone (GH). However, until now, the mechanism by which Zn2+ regulates GH biological activity remains unclear. In the current study, we first performed molecular docking between Zn2+ and porcine GH (pGH) using computational biology. We then explored the effect of Zn2+ on the GH signaling ability in the cell model expressing porcine growth hormone receptor (GHR). It was found that the phosphorylation levels of Janus kinase 2, signal transducers and activators of transcription 5/3/1, and GHR increased significantly under Zn2+ treatment, indicating that Zn2+ can enhance the signaling ability of GH/GHR. On this basis, we further explored how Zn2+ regulates the biological activity of GH/GHR. The results showed that downregulation and turnover of GHR changed under Zn2+ /pGH treatment. Zn2+ enhanced the membrane residence time of pGH/GHR and delayed GHR downregulation. Further investigation showed that the internalization dynamic of pGH/GHR was changed by Zn2+ , which prolonged the residence time of pGH/GHR in the cell membrane. These factors acted together to upregulate the signaling of GH/GHR. This study lays a foundation for further exploration of the biological effects of Zn2+ on GH.