Increased extracellular signal regulated kinases phosphorylation in the adrenal gland in response to chronic ACTH treatment

• Type: Article in International Scientific Journal
• Date: 2007

Authors

J Ferreira (Author) FMUP; Cruz C.D. (Author) FMUP; D Neves (Author) FMUP; Pignatelli, D (Author) Other

Journal

Title: Journal of Endocrinology

Vol. 192 No. 3

Pages: 647-658

ISSN: 0022-0795

Publisher: BioScientifica Ltd.

Indexing

ISI Web of Knowledge - 26 Citations

Scopus - 30 Citations

Scientific classification

CORDIS: Health sciences > Medical sciences > Medicine > Endocrinology

Other information

Authenticus ID: P-004-BHF

DOI: 10.1677/joe.1.06961

Abstract (EN): ACTH released from the pituitary acts through activation of cAMP/PKA in adrenocortical cells stimulating steroidogenesis. Although ACTH was originally thought to have anti-proliferative effects on the adrenal, recently it has been described that it could also have proliferative effects acting through other signalling cascades. This is also relevant in humans given the increased levels of ACTH occurring together with adrenal cortex hyperplasia observed in Cushing's disease and possibly in other situations such as chronic stress. One of the signalling pathways regulating cell proliferation is the extracellular signal regulated kinase (ERKs) pathway. ERKs are members of the MAPK family of cascades. They are activated by extracellular stimuli such as growth factors and mitogens, become phosphorylated through MEK1/2 and regulate a diversity of cellular processes such as proliferation and differentiation. Until now, no study addressed the effects of chronic ACTH administration on the activation of ERKs in vivo. Using rats submitted to different ACTH dosages as well as variable durations, we determined if ACTH induced ERKs activation and by establishing a parallelism with proliferating cell nuclear antigen (PCNA) expression, we aimed to demonstrate a role of ACTH-induced ERKs activation in cell proliferation. Blood was collected for hormonal analysis and the role of ACTH-induced ERKs activation in the stimulation of steroidogenesis was also studied. We confirmed that ACTH increased adrenal weight and corticosterone levels when compared with control or dexamethasone-treated animals. We also demonstrated that ACTH increases ERKs activation and PCNA expression in a time-and dose-dependent manner. When ERKs activation was blocked by the use of a specific MEK inhibitor (PD98059), there was a decrease in ACTH-induced corticosterone release and PCNA expression. We conclude that chronic ACTH induces ERKs activation and that this plays an important role in the induction of cell proliferation as well as steroidogenesis.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 12