Temporal sequence of hormonal interactions during the prereplicative phase of quiescent cultured 3T3 fibroblasts

After addition of prostaglandin F2alpha (PGF2alpha) and insulin to quiescent cultured 3T3 fibroblasts a constant lag phase of 15 hr occurs before an increased rate of cellular exit from G1 is observed. The latter process follows first order kinetics, which can be quantified by a rate constant k. The temporal relationship of the interactions of PGF2 alpha, insulin, and hydrocortisone to produce alterations in the rate of exit from G1 was investigated. PGF2alpha establishes a constant lag phase and produces alterations in the rate constant k. These two effects can be partially separated by adding two concentrations of PGF2alpha at different times. Insulin fails to establish the lag phase but can stimulate the effect of PGF2alpha when added at any time after PGF2alpha. Hydrocortisone reduces the value of k when added between 0 and 3 hr after PGF2alpha. These results show that the lag phase can beseparated into temporal regions during which hormones can interact to produce changes in the rate of cellular exit from G1.