[Modulations of human growth hormone receptor level on the cell surface]

Using a monoclonal antibody (GHRP2-88) raised against the extracellular portion of human growth hormone receptor (hGHR), the mechanisms on modulations of cellular levels of hGHR were investigated in human IM-9 cells. Upon stimulation with human growth hormone (hGH), hGHRs on the cell surface are down-regulated through internalization and degradation of hGHR. For hGHR internalization, hGH-mediated dimerization of hGHRs, but not staurosporine-sensitive phosphorylation is required. For hGHR degradation, however, staurosporine-sensitive phosphorylation is necessary. In the absence of hGH, hGHRs on the cell surface are cleaved to release human growth hormone-binding proteins (hGH-BPs), probably by a metalloprotease. In the presence of hGH, the hGH-BP release was rather decreased based on the reduction in cell surface hGHRs. Thus, the cell surface level of hGHR may be regulated post-translationally by the two mechanisms depending on the external hGH levels.