Heterogeneity of Growth Hormone (GH) Release by Individual Pituitary Adenoma Cells From Acromegalic Patients, as Determined by the Reverse Hemolytic Plaque Assay: Effects of SMS 201-995, GH-Releasing Hormone and Thyrotropin-Releasing Hormone*

Abstract

We used the reverse hemolytic plaque assay to study the dynamics of GH secretion by individual pituitary adenoma cells from eight acromegalic patients. There was a considerable variation between the adenomas with respect to the percentages of GH-secreting cells (25–78.5%) and also with respect to the amount of GH released per individual pituitary adenoma cell (mean plaque areas varying from 901–3559 μm²). The GH plaque area frequency distributions from the ade-noma cells were not normally distributed, but revealed a preponderance of small plaques, defined as those with areas smaller than the mean plaque area. The large plaques, that is those with areas larger than the mean plaque area, constituted 24–38% of the total cell population from different tumors and accounted for a large fraction (63–80%) of the total plaque area (the total amount of GH released by the adenoma cells). The somatostatin analog SMS 201–995 caused a shift in the GH plaque area frequency distributions toward smaller plaques, but had no effect on the overall percentages of GH plaque-forming cells in three of the five adenomas in which it was studied. This finding suggests that the adenoma cells from these patients that formed large plaques were preferentially inhibited by SMS 201-995. GHRH (studied in two adenomas) and TRH (studied in one adenoma) had no preferential effect on any subpopulation of adenoma cells. We conclude that GH secretion by individual somatotroph adenoma cells is highly variable both within and between ade-nomas and that SMS 201–995 has a preferential inhibitory effect on a subpopulation of adenoma cells in some adenomas.