Endocrine Abstracts

Cellular senescence is a state of permanent and stable proliferative arrest in G₁ phase of the cell cycle through activation of the p53/p21 and pRb/p16 signalling pathways. Oncogene-induced senescence (OIS) is a highly proliferative state, which mimics transformation, but this mitotic burst is gradually replaced by senescence. Several lines of evidence have implicated OIS as a vital cause of arrest of benign neoplasms. Pituitary tumors are mostly benign, non-metastatic and monoclonal neoplasms. The precise mechanisms underlying the unique indolent growth of these benign adenomas remain unknown.

Normal pituitary cells are under auto-/paracrine control of numerous growth factors. Altered expression of cytokines/growth factors and their receptors, has been observed in pituitary tumors. IL-6 plays an important role in pituitary tumor progression. IL-6 is produced by tumoral cells but is also delivered to the normal or adenoma cells through folliculo stellate (FS) cells, which mix up with the normal pituitary cells and further surround the pituitary tumors. It has been shown that IL-6 inhibits normal pituitary cell proliferation and has opposite effects in normal and tumoral pituitary cells.

IL-6 plays a key role in OIS induction indicating that IL-6 is a pleiotropic cytokine that can function as an autocrine or paracrine tumorigenic factor. The fact that IL-6 is a cytokine that participates in pituitary tumor development, in addition to the findings of its role in OIS, makes this cytokine an attractive candidate as an autocrine/paracrine stimulator of pituitary adenoma progression inducing OIS.

IL-6 maintains pituitary tumoral senescence by its autocrine action, providing a natural model of IL-6 mediated adenoma OIS, which explains the benign nature of these abundant adenomas.