cAMP inhibits IGF-I-induced mitogenesis in fetal rat brown adipocytes: Role of p21 ras

Dibutyryl cAMP (DBcAMP) inhibited insulin-like growth factor I (IGF-I)- induced DNA synthesis of rat fetal brown adipocyte primary cultures. Its mitogenic inhibitory capacity, measured as [3H]thymidine incorporation into acid-precipitable material, was dose-dependent, being maximal at 0.5 mM. The entry of cells into S + G2/M phases of the cell cycle and the increase in cell number induced by IGF-I were partially inhibited by DBcAMP at 24 h and totally prevented at 48 h. DBcAMP inhibited the mRNA expression of c-myc induced by IGF-I at 2 h. Moreover, DBcAMP inhibited in parallel H-ras mRNA expression, p21 ras, and proliferating cellular nuclear antigen protein content induced by IGF-I at 24 and 48 h of culture, respectively, suggesting the involvement of p21 ras in the progression of fetal brown adipocytes through the S phase of the cell cycle and DNA synthesis.This work was supported by Grant SAF93/0206 from CICYT, Spain. T. Teruel was a recipiebt of a fellowship from Comunidad Autónoma de Madrid, Spain.Peer Reviewe