Kinetics of cAMP inhibition of DNA synthesis in bovine adrenocortical cells

Abstract

cAMP-treated bovine adrenocortical cells are arrested in the G 1 phase of the cell cycle. Removal of serum also arrests bovine adrenocortical cells in G 1. In the presence of cAMP, serum and fibroblast growth factor stimulate increases in medium cell volume, but DNA synthesis is not initiated. Under these conditions cAMP increases steroidogenic capacity 7- to 10-fold as assessed by metabolism of pregnenolone to fluorogenic steroids. When the kinetics of entry of cells into S phase are quantitated, serum- and FGF-treated cells initiate DNA synthesis at an exponential rate after a 12-h lag. In contrast when cAMP is removed, cells immediately initiate DNA synthesis without a lag at a similar exponential rate .(6.3 and 5.3% of the cells entering S/h). In the presence of growth factors, cAMP-treated bovine adrenocortical cells are thus hypertrophied with increased steroidogenic capacity, but are reversibly arrested at the G 1/S boundary. These findings suggest that cAMP arrests cell replication by mechanisms distinct from those of serum deprivation.