Cyclic adenosine 3'-5'-monophosphate (cAMP) exerts proliferative and anti-proliferative effects in pituitary cells of different types by activating both cAMP-dependent protein kinase A (PKA) and exchange proteins directly activated by cAMP (Epac)

E. Vitali, E. Peverelli, E. Giardino, M. Locatelli, G. B. Lasio, P. Beck-Peccoz, A. Spada, A. G. Lania, G. Mantovani

Research output: Contribution to journalArticle

Abstract

In the pituitary the activation of cyclic adenosine 3'-5'-monophosphate (cAMP) dependent pathways generates proliferative signals in somatotrophs, whereas in pituitary cells of other lineages its effect remains uncertain. Moreover, the specific role of the two main cAMP effectors, protein kinase A (PKA) and exchange proteins directly activated by cAMP (Epac), has not been defined. Aim of this study was to investigate the effect of cAMP on pituitary adenomatous cells proliferation and to identify PKA and Epac differential involvement. We found that cAMP increased DNA synthesis and cyclin D1 expression in somatotropinomas, whereas it reduced both parameters in prolactinomas and nonfunctioning adenomas, these effects being replicated in corresponding cell lines. Moreover, the divergent cAMP effects were mimicked by Epac and PKA analogs, which activated Rap1 and CREB, respectively. In conclusion, we demonstrated that cAMP exerted opposite effects on different pituitary cell types proliferation, these effects being mediated by both Epac and PKA.

Original languageEnglish
Pages (from-to)193-202
Number of pages10
JournalMolecular and Cellular Endocrinology
Volume383
Issue number1-2
DOIs
Publication statusPublished - Mar 5 2014

Keywords

  • CAMP
  • CAMP-dependent protein kinase A (PKA)
  • Exchange proteins directly activated by cAMP (Epac)

ASJC Scopus subject areas

  • Endocrinology
  • Molecular Biology
  • Biochemistry

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