Pituitary gene expression differs in D-galactose-induced cell senescence and steroid-induced prolactinomas

Abstract

In general, pituitary tumors are benign with low mitotic activity. Premature senescence has been considered to be a significant mechanism underlying this uniquely benign pituitary tumor. The present study aims to compare the expression of the associated proteins involved in premature senescence pathways among normal, aging and pituitary adenoma cells. We successfully induced the aging pituitary using continuous D-galactose (D-gal) injection as well as a prolactin-secreting pituitary tumor via diethylstilbestrol implants. Compared with normal pituitary cells, the aging pituitary tissues revealed increased expression of IL-6, C/EBPβ, p53, p21 and p16 and decreased expression of pituitary tumor transforming gene. In contrast, the expression of IL-6, p21 and p16 was decreased in pituitary tumor cells compared with normal pituitary tissues. Taken together, multiple pathways including IL-6/C/EBPβ, p53/p21 and p16 were activated in aging pituitary cells in response to D-gal treatment. However, all these pathways were immune to pituitary tumors treated by chronic estrogen. The findings and the involvement of cytokines in a highly prevalent natural disease model (pituitary adenomas) indicate a potential use of this pathway as a target for effective therapy for tumor silencing and prevention of adenoma progression towards malignancy.