ACTH increases expression of c-fos, c-jun and beta-actin genes in the dexamethasone-treated rat adrenals.

Abstract

Our recent finding that ACTH increases c-fos mRNA in the adrenal gland of hypophysectomized rats indicates that the gene product FOS may play an important role(s) in mediating the action of ACTH. However, hypophysectomy employed in that study causes the disappearance of trophic hormones other than ACTH and may modify the effect of ACTH. Thus, in the present investigation, dexamethasone-treated rats were used. Since FOS functions only when it dimerizes with JUN (the product of c-jun gene), the changes in the levels of c-fos and c-jun mRNAs were studied together with that of beta-actin mRNA which is also affected by ACTH. Northern blot analysis was employed to determine the mRNA levels. It was demonstrated that ACTH increases the mRNAs coding c-fos and c-jun in the adrenal glands of dexamethasone-treated, ACTH-suppressed rats. The c-fos mRNA was not detectable before ACTH administration. After ACTH administration, the mRNA levels were transiently increased, the maximum level being observed at 30 min after ACTH. At 180 min post ACTH, the level returned to the unstimulated level. The mRNA coding c-jun was detectable before ACTH administration and it also increased rapidly after ACTH with maximal stimulation at 30 min. However, the mRNA level at 180 min post ACTH was still higher than the unstimulated level. The changes in beta-actin mRNA were approximately the same as those of c-jun mRNA. These results suggest that increased expression of c-fos, c-jun and beta-actin genes by ACTH may play an important role in mediating its action on the adrenals.