Cyclic AMP-independent effects of ACTH on of the rat adrenal cortex

The aim of the present paper is to point out the complexity of ACTH action in glomerulosa cells of the adrenal cortex. We demonstrate that the increas e in cAMP production induced by ACTH is the result of a balance between act ivation of adenylyl cyclase and direct modulation of a PDE2 phosphodiesteas e activity, an effect mediated by inhibition of cGMP content. Moreover, Ca2 + is essential for cAMP production and aldosterone secretion, but its exact primary action is not clearly determined. We recently described that ACTH activated a chloride channel, via the Ras protein, which can be involved in steroidogenesis. ACTH also increases tyrosine phosphorylation of several p roteins. These data, together with those of phospholipase C activation, ind icate that ACTH action in the adrenal is complex, and most certainly not li mited to cAMP production, in particular for the low concentrations of the h ormone. Some years ago, cAMP was considered to be the unique second messenger of AC TH action; now it becomes more and more evident that ACTH triggers complex signaling pathways using several second messengers in a closely interacting way. The most predominant point is that these signals are observed for low concentrations of ACTH. (C) 1999 Elsevier Science Ltd. All rights reserved .