Endocrine Abstracts

Introduction: In many tissues angiotensin peptides acts as the auto/paracrine growth factors. Their effects are dependent on activation of various intracellular signaling pathways, including mitogen-activated protein kinases (MAPK).

Angiotensin II (ang II) is the best known angiotensin peptide. The ang II derivatives, angiotensin III (ang III) and angiotensin IV (ang IV) posses biological activity as well. Both ang II and ang IV are known to promote the proliferation of rat prolactinoma cells in vitro and rat anterior pituitary cells in vivo. The role of ang IV degradation products, angiotensin 4–8 (ang 4–8) and angiotensin 5–8 (ang 5–8) in the regulation of cellular growth has not already been investigated.

Aim: In our study we examined the influence of ang 4–8 and ang 5–8 on the GH3 cells (rat pituitary lactosomatotroph tumor cells line) proliferation and the possible role of two MAPK pathways (p44/42 and p38) in ang 5–8 regulatory action.

Material and Methods: GH3 cells were cultured in F-10 medium and then plated at 96-multiwell plates (10×10³ cells/well). After 12 hours of preincubation cells underwent to 72-hours treatment either with ang 4–8 or ang 5–8 alone or with the combination of ang 5–8 and p44/42 MAPK-kinase or p38 MAPK inhibitor (PD98059 or SB203580 respectively). Cell proliferation was evaluated using two colorimetric assays: based on the measurement of cell activation and on the BrdU incorporation during DNA synthesis.

Results: Ang 4–8 and ang 5–8 decreased both the cell activation and BrdU incorporation in GH3 cells culture. SB203580 prevented only the ang 5–8-induced inhibition of cells activation. Non of ang 5–8 effects was abolished by PD98059.

Conclution: Ang 4–8 and ang 5–8 inhibit GH3 cell proliferation. This mechanism is independent of both MAPK p44/42 and MAPK p38. They probably exert additional proapoptotic effect, mediated by MAPK p38.