N-POMC1-28 increases cyclin D expression and inhibits P27(kip1) in the adrenal cortex

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 previ...

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Bibliographic Details
Published in:Molecular and cellular endocrinology 2013-05, Vol.371 (1-2), p.166-173
Main Authors: de Mendonca, Pedro O R, Liria, Cleber W, Machini, Maria Teresa, Lotfi, Claudimara F P
Format: Article
Language:English
Subjects:
Adrenal Cortex - drug effects
Adrenal Cortex - metabolism
Adrenocorticotropic Hormone - metabolism
Adrenocorticotropic Hormone - pharmacology
Animals
Apoptosis Regulatory Proteins - metabolism
Cell Cycle Checkpoints
Cell Cycle Proteins - biosynthesis
Cell Cycle Proteins - metabolism
Cell Proliferation
Cyclin D - biosynthesis
Cyclin D1 - biosynthesis
Cyclin D2 - biosynthesis
Cyclin D3 - biosynthesis
Cyclin-Dependent Kinase Inhibitor p27 - biosynthesis
Down-Regulation
Male
Peptide Fragments - metabolism
Peptide Fragments - pharmacology
Pro-Opiomelanocortin - metabolism
Pro-Opiomelanocortin - pharmacology
Rats
Rats, Sprague-Dawley
Up-Regulation
Zona Glomerulosa - metabolism
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Summary: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.
ISSN:1872-8057
DOI:10.1016/j.mce.2012.11.017