{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T15:35:17Z","timestamp":1791214517087,"version":"4.1.0"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"3","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":["eur j endocrinol"],"published-print":{"date-parts":[[2005,9]]},"abstract":"<jats:p><jats:italic>Objectives<\/jats:italic>: Although several lines of evidence suggest that the overall effects of the ACTH receptor, melanocortin 2 receptor (MC2-R), mediated signal transduction on adrenocortical growth and tumorigenesis are anti-proliferative, activation of MC2-R induces mitogens like jun, fos, and myc and activates the MAPK pathway.<jats:italic>In vivo<\/jats:italic>, potential effects of endogenous ACTH on adrenal tumori-genesis can not be separated from effects of other POMC derived peptides.<\/jats:p><jats:p><jats:italic>Methods<\/jats:italic>: Murine adrenocortical tumor cells that lack MC2-R expression (Y6<jats:sup>pcDNA<\/jats:sup>) and Y6 cells stablely transfected with MC2-R (Y6<jats:sup>MC2-R<\/jats:sup>) were generated. Presence of functional MC2-R was demonstrated by RT-PCR and Western blot using an antibody for phosphorylated CREB. As a syngenic tumor model, LaHeF1\/J mice simultaneously received 10<jats:sup>7<\/jats:sup>Y6<jats:sup>MC2-R<\/jats:sup>and Y6<jats:sup>pcDNA<\/jats:sup>subcutaneously, giving rise to MC2-R positive and negative tumors within the same animal. Animals were treated for 3 weeks in groups of 12 according to the following schedule: group A, control animals receiving saline injection; group B, animals receiving 5.7 ng\/injection of a slow release formula of ACTH 1-24 administered i.p. three times a week (aiming at a low physiologic dose); and group C, animals receiving 57 ng\/injection of ACTH 1-24 (high physiological dose).<\/jats:p><jats:p><jats:italic>Results<\/jats:italic>: Twenty days of ACTH 1-24 treatment did not significantly affect corticosterone levels, endogenous ACTH levels or adrenal and thymus weight compared with saline injection. However, ACTH 1-24 treatment of group B and C mice significantly reduced tumor weight in MC2-R positive tumors in a dose dependent manner (<jats:italic>P<\/jats:italic>= 0.03), while no significant difference in tumor mass was observed in MC2-R negative tumors. PCNA and TUNEL staining, together with morphological characterization, demonstrated that these<jats:italic>in vivo<\/jats:italic>effects were due to reduced proliferation, while apoptosis and cellular hypertrophy within the tumor remained unchanged.<\/jats:p><jats:p><jats:italic>Conclusion<\/jats:italic>: MC2-R expression is associated with a less aggressive adrenal tumor phenotype and anti-proliferative effects can be amplified through stimulation with physiological doses of ACTH.<\/jats:p>","DOI":"10.1530\/eje.1.01983","type":"journal-article","created":{"date-parts":[[2005,8,30]],"date-time":"2005-08-30T18:44:00Z","timestamp":1125427440000},"page":"435-444","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":26,"title":["ACTH 1-24 inhibits proliferation of adrenocortical tumors in 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