A 3',5'-cyclic adenosine monophosphate-dependent pathway is responsible for a rapid increase in c-fos messenger ribonucleic acid by adrenocorticotropin.

Abstract

ACTH rapidly and transiently increases c-fos mRNA in the rat adrenals in vivo. The present investigation was undertaken in order to determine what kind(s) of second messenger systems is involved in this increase. Rat adrenal cells were grown in monolayers in Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum. After 2 days of culture, cells were treated with ACTH and various agents alone or in combination. The amount of c-fos mRNA was determined by dot blot hybridization and corticosterone levels in the media were measured by RIA. ACTH (300 pg/ml) increased c-fos mRNA transiently with a peak level after 60 min. A similar increase was observed when (Bu)2cAMP (1 mM) was substituted for ACTH. Pretreatment with N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinoline-sulfonamide (H-89), a selective inhibitor of cAMP-dependent protein kinase, suppressed both basal and ACTH-increased c-fos mRNA. H-89 also suppressed corticosterone production. On the other hand, neither 12-O-tetradecanoyl-phorbol-13-acetate (100 ng/ml) nor elevated potassium ion (50 mM) affected the amount of c-fos mRNA and corticosterone production. Furthermore, pretreatment with cycloheximide (5 micrograms/ml) increased both basal and ACTH-increased c-fos mRNA. These results indicate that ACTH increases c-fos mRNA by phosphorylation of preexisting trans-acting factor(s) via cAMP-dependent protein kinase in common with steroidogenesis.

Endothelin‐1[1–31], acting as an ETA‐receptor selective agonist, stimulates proliferation of cultured rat zona glomerulosa cells

“…Evidence indicates that, in addition to TK, G protein‐coupled receptors can activate the MAPK cascade [21], through both protein kinase‐C (PKC)‐ [22–24] and PKA‐dependent pathways [24,25]. Accordingly, angiotensin‐II was found to stimulate mitogenesis and MAPK activity in bovine ZG cells via a PKC‐dependent and a PKC‐independent pathway [26], and cyclic‐AMP was shown to activate MAPK and to enhance proliferation of ZG cells [27]. Our data demonstrate the involvement of the PKC pathway in the MAPK‐mediated ZG proliferogenic action of ET‐1[1–31].…”

Adrenomedullin Enhances Cell Proliferation and Deoxyribonucleic Acid Synthesis in Rat Adrenal Zona Glomerulosa: Receptor Subtype Involved and Signaling Mechanism

“…41 and 42). Accordingly, ET-1 and Ang-II stimulate mitogenesis and MAPK activity of ZG cells through PLC/PKC-independent and -dependent pathways (24,33), and cAMP induces MAPK activation and cell proliferation in many cell systems, including ZG cells (31), although the ability of ACTH to stimulates MAPK in rat ZG cells has been recently denied (46). Accordingly, ET-1 and Ang-II stimulate mitogenesis and MAPK activity of ZG cells through PLC/PKC-independent and -dependent pathways (24,33), and cAMP induces MAPK activation and cell proliferation in many cell systems, including ZG cells (31), although the ability of ACTH to stimulates MAPK in rat ZG cells has been recently denied (46).…”

Signaling Pathways in Adrenocortical Cancer

“…However, prolonged treatment (18‐24 hours) leads to an arrest of cells before S phase, so that the overall effect is an inhibition of cell cycle progression 34. At the molecular level, ACTH or cAMP treatment leads to a rise in c‐fos and c‐jun mRNA, but appears to inhibit the accumulation of c‐myc 34,36,37. This blockade of c‐myc appears sufficient to prevent cells from entering the cell cycle 37…”

“…34 At the molecular level, ACTH or cAMP treatment leads to a rise in c-fos and c-jun mRNA, but appears to inhibit the accumulation of c-myc. 34,36,37 This blockade of c-myc appears sufficient to prevent cells from entering the cell cycle. 37 Furthermore, there is ample evidence in adrenal cells that ACTH, acting through the PKA pathway, is able to inhibit proliferative signals initiated through other signaling pathways.…”