Development of abnormal parathyroid cell function during monolayer culture and its relation to cellular hypertrophy and proliferation.

Primary cultures of adult bovine parathyroid cells grown for up to 8 days were used to study the relationship between regulation of parathyroid hormone (PTH) release, cytoplasmic Ca2+ (Ca2+i) and cell growth. Cell counting indicated that proliferation was inversely proportional to the seeding density. The culture was associated with cell enlargement without apparent relation to the proliferation rate. Moreover, flow cytometric analysis of the DNA distribution excluded that the hypertrophy was due to a high proportion of the cells being in the S and G2 stages of the cell cycle. With progressive time in culture there was a gradual deterioration of the ability of increasing concentrations of extracellular Ca2+ to suppress PTH secretion and raise Ca2+i. This functional dedifferentiation developed to the same extent despite considerable differences in proliferation rates. The data show that parathyroid cells in monolayer culture develop functional and some of the morphological characteristics of parathyroid cells from patients with hyperparathyroidism and that the functional abnormality seems to be related to hypertrophy but not to proliferation of the cells.