title: N-POMC1-28 increases cyclin D expression and inhibits P27(kip1) in the adrenal cortex.
abstract: The Adrenocorticotropic hormone (ACTH) and Pro-opimelanocortin (POMC) 1-28N-terminal peptide (N-POMC(1-28)) have been shown to act as an adrenal mitogen in vivo. A possible role for cyclin E in the zona glomerulosa (ZG) proliferation, following ACTH and/or N-POMC(1-28) administration, has been previously demonstrated. In this study, we investigated the effect of ACTH and N-POMC(1-28) on the expression of adrenal cortex proteins related to cell cycle control such as cyclins D and P27(kip1). The administration of N-POMC upregulated cyclin D1 and D2 expression in the outer zone of the adrenal cortex; cyclin D3 expression was upregulated in the cortex inner zone even after administration of ACTH. Both ACTH and N-POMC peptides induced a decrease in the P27(kip1) expression in the ZG. These novel findings suggest that the POMC-derivate peptides, ACTH and N-POMC, promote proliferation in the adrenal cortex by upregulating the D2 and D3 cyclins and downregulating the P27(kip1) expression.
authors.affiliation: Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-900, Brazil.
authors.forename: Pedro O R
authors.initials: PO
authors.lastname: de Mendonca
authors.forename: Cleber W
authors.initials: CW
authors.lastname: Liria
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Machini
authors.forename: Claudimara F P
authors.initials: CF
authors.lastname: Lotfi
mesh_terms: D000302:Adrenal Cortex / Q000187:drug effects / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D059447:Cell Cycle Checkpoints; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000378:metabolism; D049109:Cell Proliferation; D056741:Cyclin D / Q000096:biosynthesis*; D019938:Cyclin D1 / Q000096:biosynthesis; D056742:Cyclin D2 / Q000096:biosynthesis; D056743:Cyclin D3 / Q000096:biosynthesis; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000096:biosynthesis*; D015536:Down-Regulation; D008297:Male; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology*; D011333:Pro-Opiomelanocortin / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation; D015384:Zona Glomerulosa / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; C530106:Ccnd1 protein, rat; C486197:Ccnd2 protein, rat; C534698:Ccnd3 protein, rat; C493962:Cdkn1b protein, rat; D018797:Cell Cycle Proteins; D056741:Cyclin D; D056742:Cyclin D2; D056743:Cyclin D3; C553466:N-POMC (1-28); D010446:Peptide Fragments; D019938:Cyclin D1; D050760:Cyclin-Dependent Kinase Inhibitor p27; D011333:Pro-Opiomelanocortin; D000324:Adrenocorticotropic Hormone