THE RELATIONSHIP BETWEEN GROWTH-HORMONE (GH) MESSENGER-RIBONUCLEIC-ACID LEVELS AND HORMONE-RELEASE FROM INDIVIDUAL CELLS DERIVED FROM HUMAN GH-SECRETING PITUITARY-ADENOMAS

GH mRNA expression and GH release by individual cells derived from four GH-secreting pituitary adenomas were studied by in-situ hybridization and the reverse haemolytic plaque assay, respectively. In addition the percentage of PRL mRNA-containing cells was determined in these cells suspensions. The percentages of GH mRNA-containing cells varied between 52 and 89 while the percentages of GH plaque forming cells varied between 25 and 77. Frequency distributions of GH mRNA levels in individual cells and of individual GH plaque areas showed a majority of the cells having low GH mRNA levels and secreting low amounts of GH respectively, while there is a low proportion of cells expressing high GH mRNA levels and forming large GH plaques. There was a significant correlation between the GH mRNA levels and the GH plaque areas of individual cells from the four adenomas (P < 0.001). The percentage of PRL mRNA-containing cells in the four different adenomas amounted to < 1,5,2 and 18. Cultured cells from the adenomas consisting of 5 and 18% PRL mRNA-containing cells also contained and released measurable amounts of PRL. Our data show that individual cells from GH-secreting pituitary adenomas are heterogeneous with respect to GH mRNA expression, a small proportion of the cells expressing a high amount of GH mRNA. The heterogeneity in GH mRNA expression is correlated with the heterogeneity in GH release. These observations suggest that a considerable part of GH secreted from a GH-secreting pituitary adenoma is produced by a minority of the GH-secreting tumour cell population. This might be a basis for the disappointing degree of tumour shrinkage which is observed in most acromegalic patients treated with the somatostatin analogue SMS 201-995.