Clonal analysis of a 5-azacytidine-induced specific increase in growth hormone production by rat pituitary cells.

The nucleoside analog, 5-azacytidine (5-azaCR) which causes genomic hypomethylation in many cell types, increased GH production by GH4C1 rat pituitary cells 3-5 fold. This increased GH production was independent of changes in prolactin (PRL) synthesis by the same cells; it occurred at 10-fold lower 5-azaCR concentrations than those which increased the synthesis of PRL. Elevated GH production persisted for more than 20 population doublings after removal of 5-azaCR from the culture medium, indicating that the induced change was phenotypically stable. GH production remained responsive to stimulation by cortisol in 5-azaCR-treated cells. Clonal analysis demonstrated that the increased GH production was due to a higher incidence of cells in the population which made GH at an enhanced rate.