Distribution of cells expressing Jun and Fos proteins and synthesizing DNA in the adrenal cortex of hypophysectomized rats: regulation by ACTH and FGF2

Abstract

Protein expression of the early response genes, jun and fos, has been suggested to play an important role in the in vitro and in vivo proliferation of adrenal cells. To elucidate the immunolocalization of proliferative cells and the patterns of adrenal gland expression of members of the activating protein-1 (AP-1) family of oncogenes, we used hypophysectomized rats. The effects of adrenocorticotropic hormone (ACTH) and fibroblast growth factor 2 (FGF2) on Fos and Jun protein expression were investigated, and DNA synthesis was assessed by using bromodeoxyuridine (BrdU) incorporation. No change was detectable in the adrenal cortex at 2 days after hypophysectomy, although a reduction occurred in the number of BrdU-positive cells in the zona fasciculata. This hypophysectomy-induced early phase of adrenal cortex atrophy in the zona fasciculata was correlated with JunB protein induction, suggesting the formation of an inhibitory AP-1 complex. Accumulation of c-Jun/JunD and c-Fos/FosB, but not of JunB, in the zona fasciculata and zona reticularis implied that, after ACTH stimulation, these proteins were the principal AP-1 components in these zones. In these same zones, ACTH increased BrdU-positive cell counts, indicating that the composition of the AP-1 complex in these zones was proliferation-related. However, FGF2 induced an antagonistic modulation of the response to ACTH, by reducing the numbers of Jun-/Fos-positive cells and inhibiting DNA synthesis. Our results implicate the AP-1 family of transcription factors (in particular, the dynamics within the Jun protein family) in the regulation of cell control during ACTH-induced proliferation of the adrenal cortex.