GROWTH-HORMONE RECEPTOR EXPRESSION IN THE NUCLEUS AND CYTOPLASM OF NORMAL AND NEOPLASTIC-CELLS

Growth hormone (GH) exerts its regulatory functions in controlling met abolism, balanced growth and differentiated cell expression by acting on specific receptors which trigger a phosphorylation cascade, resulti ng in the modulation of numerous signalling pathways dictating gene ex pression. A panel of five monoclonal antibodies was used in mapping th e presence and somatic distribution of the GH receptor by immunohistoc hemistry in normal and neoplastic tissues and cultured cells of human, rat and rabbit origin. A wide distribution of the receptor was observ ed in many cell types. Not all cells expressing cytoplasmic GH recepto rs displayed nuclear immunoreactivity. In general, the relative propor tion of positive cells and intensity of staining was higher in neoplas tic cells than in normal tissue cells. Immunoreactivity showed subcell ular localisation of the GH receptor in cell membranes and was predomi nantly cytoplasmic, but strong nuclear immunoreaction was also apparen t in many instances. Intense immunoreactivity was also observed in the cellular Golgi area of established cell lines and cultured tissue-der ived cells in exponential growth phase, indicating cells are capable o f GH receptor synthesis. The presence of intracellular GH receptor, pr eviously documented in normal tissues of mostly animal origin, is the result of endoplasmic reticulum and Golgi localisation. Heterogeneity of immunoreactivity was found in normal and neoplastic tissue with a v ariable range of positive cells. The nuclear localisation of immunorea ctivity is the result of nuclear GH receptor/binding protein, identica lly to the cytosolic and plasma GH-binding protein, using a panel of f ive monoclonal antibodies against the GH receptor extracellular region . The expression of GH receptors, not only on small proliferating tumo ur cells such as lymphocytes, but also on well differentiated cells in cluding keratinocytes, suggests that GH is necessary not only for diff erentiation of progenitor cells, but also for their subsequent clonal expansion, differentiation and maintenance.