Role of the PPAR-γ System in Normal and Tumoral Pituitary Corticotropic Cells and Adrenal Cells

Massimo Mannelli, Giulia Cantini, Giada Poli, Monica Mangoni, Gabriella Nesi, Letizia Canu, Elena Rapizzi, Elisa Borgogni, Tonino Ercolino, Valentina Piccini, Michaela Luconi
2010 Neuroendocrinology  
nificant inhibition of tumor growth in the xenograft tumor models. In addition, since RGZ can reduce ACTH and corticosterone secretion in mouse corticotropic pituitary tumors, both RGZ and PIO have been used in the treatment of Cushing's disease with variable but generally unsatisfactory results. Discrepancies in the antitumor effects of TZD observed between successful preclinical and unsuccessful clinical studies may be particularly due to differences in treatment duration and doses used.
more » ... duction PPAR-␥ is a member of the nuclear hormone receptor superfamily of transcription factors, widely expressed in the organism, including adipose, vascular and immune cells. Besides its well-known role in the regulation of metabolism, PPAR-␥ has also recently emerged as a key regulator of inflammatory and immune responses [1] as well as of proliferation, differentiation and apoptosis in nor-Abstract PPAR-␥ is a member of the nuclear hormone receptor superfamily of transcription factors, whose thiazolidinedione ligands (TZD) have been recently demonstrated to also possess anticancer properties in addition to their well-known insulin-sensitizer and glucose/lipid regulation activity. In this minireview, we summarize the current knowledge on PPAR-␥ in normal and tumoral corticotropic pituitary and adrenal cells. The receptor expression has been shown in ACTH-secreting cells in both normal and adenomal pituitary as well as in normal and tumor adrenal cortex. Preclinical studies conducted both in vitro on tumor cells and in vivo on xenograft tumor models obtained by subcutaneous injection of cancer cells have evidenced the anticancer properties of TZD, in particular rosiglitazone (RGZ) and pioglitazone (PIO). In both pituitary and adrenocortical cancer, RGZ treatment results in inhibition of cell proliferation, through G0/G1 cellcycle arrest and induction of cell apoptosis, leading to sig-
doi:10.1159/000314312 pmid:20829614 fatcat:me2etfog2bhhvnnoto4lsg2fr4