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.

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. - In: MOLECULAR AND CELLULAR ENDOCRINOLOGY. - ISSN 0303-7207. - 383:1-2(2014), pp. 193-202.

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
Primo
;
E. Peverelli
Secondo
;
E. Giardino;M. Locatelli;P. Beck-Peccoz;A. Spada;A.G. Lania
;
G. Mantovani
Ultimo
2014

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.
CAMP; CAMP-dependent protein kinase A (PKA); Exchange proteins directly activated by cAMP (Epac); Adenoma; Animals; Cell Proliferation; Cyclic AMP; Cyclic AMP Response Element-Binding Protein; Cyclic AMP-Dependent Protein Kinases; Cyclin D1; Gonadotrophs; Guanine Nucleotide Exchange Factors; Humans; Lactotrophs; Pituitary Gland; Pituitary Neoplasms; Prolactinoma; Protein Subunits; Rats; Signal Transduction; Somatotrophs; rap1 GTP-Binding Proteins; Gene Expression Regulation, Neoplastic; Endocrinology; Molecular Biology; Biochemistry
Settore MED/13 - Endocrinologia
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/459957
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