TUMORIGENESI IPOFISARIA E INQUINAMENTO AMBIENTALE DA XENOBIOTICI: STUDI DI BIOLOGIA CELLULARE E MOLECOLARE SULLA VIA DI SEGNALE DELL'ARYL-HYDROCARBON RECEPTOR E TRASLAZIONE ALLA SALUTE UMANA E ALL'ESPRESSIONE CLINICA DEI TUMORI IPOFISARI

Pituitary tumors are a endocrine disease with benign neoplastic behaviour but significant clinical burden. As yet, little is known on the influence of genetic or environmental factors on their development although some evidence has accrued linking endocrine pollutants to pituitary tumors. In particular, experimental studies have shown that endocrine disruptors affect secretion and growth in rat pituitary tumoral cell lines while, in man, epidemiological data established a link between pollution and pituitary tumors. Aim of the present study is to verify whether endocrine disruptors affect normal rat pituitaries and human pituitary tumors
in vitro
. In detail, human pituitary adenoma and normal rat pituitary primary cultures will be established and incubated with parabens, xenoestrogens, phenols, phtalates and polycyclic aromatic hydrocarbons and changes in pituitary hormone synthesis and secretion, e.g., growth hormone (GH), prolactin, alfa subunit, and cell proliferation assessed. In addition, proteins and RNA collected during the incubation will be sent to participating Units for quantification of estrogen and progesterone receptor, somatostatin receptor, thyroid hormone receptor, aryl hydrocarbon receptor mRNA and interleukin levels. Immunometric assays will be used for peptide quantification, quantitative PCR for quantification of gene synthesis and cell proliferation assessed with appropriate apoptosis/viability commercial kits. Results obtained from this collaborative study will establish whether xenobiotics exert significant effects on the normal rat pituitary or on human pituitary adenomas
in vitro
and thereby contribute to increased knowledge on the relationship between pollutants and pituitary tumors.