Abstract
The identity of the pro-opiomelanocortin (POMC)-derived mitogen in the adrenal cortex has been historically controversial. We have used well-established in vivo models, viz., hypophysectomized (Hyp) or dexamethasone (Dex)-treated rats, to study the effect of the synthetic modified peptide N-terminal POMC (N-POMC1–28) on DNA synthesis in the adrenal cortex, as assessed by BrdU incorporation and compared with adrenocorticotropic hormone (ACTH). We evaluated the importance of disulfide bridges on proliferation by employing N-POMC1–28 without disulfide bridges and with methionines replacing cysteines. Acute administration of synthetic modified N-POMC1–28 distinctly increased DNA synthesis in the zona glomerulosa and zona fasciculata, but not in the zona reticularis in Hyp rats, whereas in Dex-treated rats, this peptide was effective in all adrenal zones. ACTH administration led to an increase of BrdU-positive cells in all adrenal zones irrespective of the depletion of Hyp or Dex-POMC peptides. The use of the ACTH antagonist, ACTH7–38, confirmed the direct participation of ACTH in proliferation. Two different approaches to measure apoptosis revealed that both peptides similarly exerted a protective effect on all adrenocortical zones, blocking the apoptotic cell death induced by hypophysectomy. Thus, ACTH1–39 and N-POMC1–28 have similar actions suggesting that the disulfide bridges are important but not essential. Both peptides seem to be important factors determining adrenocortical cell survival throughout the adrenal cortex, reinforcing the idea that each zone can be renewed from within itself.
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Acknowledgements
We are grateful to Dr. Maria Aparecida Juliano from the Department of Biochemistry and Biophysics of the Federal University of São Paulo (UNIFESP) for the synthesis of N-POMC peptides and to Dr. Marina Baquerizo Martinez for technical assistance with measurements of the circulating plasma ACTH.
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The authors declare no conflicts of interest to prejudice the impartiality of the research reported.
T.E.P.T. and P.O.R.M. are recipients of scholarships from the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, Foundation for the Support of Research in the State of São Paulo); C.F.P.L. received funding from FAPESP, from the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, The National Council for Scientific and Technological Development), and from the Pró-Reitoria de Pesquisa da Universidade de São Paulo (University of São Paulo Dean’s Office for Research Projects).
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Torres, T.E.P., de Mendonça, P.O.R. & Lotfi, C.F.P. Synthetic modified N-POMC1–28 controls in vivo proliferation and blocks apoptosis in rat adrenal cortex. Cell Tissue Res 341, 239–250 (2010). https://doi.org/10.1007/s00441-010-0998-0
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DOI: https://doi.org/10.1007/s00441-010-0998-0