N-POMC1–28 increases cyclin D expression and inhibits P27kip1 in the adrenal cortex

Abstract

The Adrenocorticotropic hormone (ACTH) and Pro-opimelanocortin (POMC) 1–28N-terminal peptide (N-POMC1–28) 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-POMC1–28 administration, has been previously demonstrated. In this study, we investigated the effect of ACTH and N-POMC1–28 on the expression of adrenal cortex proteins related to cell cycle control such as cyclins D and P27kip1. 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 P27kip1 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 P27kip1 expression.