Differences between the growth regulatory pathways in primary rat adrenal cells and mouse tumor cell line.

In this study, DNA synthesis, phosphorylation of ERK1/2 and CREB proteins, as well as induction of c-Fos protein, were examined in rat adrenocortical, glomerulosa and fasciculata/reticularis cells, as well as in the Y1 cell line. We found that FGF2 was mitogenic only in glomerulosa cells and although ACTH did not activate ERK1/2, it did activate CREB protein, indicating efficient transduction of signals initiated in the ACTH receptors of rat adrenocortical cells. The FGF2 activated ERK1/2 in rat adrenal cells by a mechanism that might be modulated by upstream PKA pathway phosphorylation of MEK and despite the nonmitogenic effect of ACTH on rat adrenal cells it effectively induces c-Fos protein. The results presented herein describe distinct differences between the ACTH and FGF2 signal transduction mechanisms seen in adrenocortical cells and those observed in the Y1 cell line, indicating that, in vitro, ACTH blockage of the mitogenic effect occurs in normal adrenal cells after induction of c-Fos protein.